Clinical Trials List
Protocol NumberPN-301-22
2022-04-01 - 2026-12-31
Phase II
Recruiting6
A Phase 2 Study to Evaluate the Safety and Immunological Efficacy of Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients with HER2 Expressing Gastric Cancer (CORNERSTONE-003)
-
Sponsor
novotech
-
Trial scale
Taiwan Multiple Center
-
Update
2025/11/06
Investigators and Locations
Co-Principal Investigator
- 王秀慈 無
- Chi-Ching Chen 無
- 邱昌芬 無
- Che-Hung Lin 無
- 邱昌芬 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chien-An Liu 無
- Chung-Pin Li 無
- Yee Chao 無
- Yi-Ping Hung 無
- 姜乃榕 無
- Yun-Cheng Hsieh 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 余紹銘 無
- 陳建銘 無
- 徐執中 無
- Wen-Chi Shen 無
- 黃文冠 無
- Jen-Shi Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Stomach cancer
Objectives
Stomach cancer
Test Drug
AST 301/pNGVL3 hICDLEUKINE® (sargramostim)
Active Ingredient
pNGVL3 hICD
Sargramostim
Sargramostim
Dosage Form
injection
injection
injection
Dosage
167 μg /mL
100 μg /mL
100 μg /mL
Endpoints
Safety and Tolerability: Classified according to the National Cancer Institute's Commonly Used Adverse Event Assessment Criteria (NCI CTCAE) version 5.0, regardless of causality or correlation.
• Vital Signs
• Physical Examination
• Electrocardiogram (ECG)
• Laboratory Tests
• Adverse Events (AEs)
• Treatment-Induced Adverse Events (TEAEs)
• Serious Adverse Events (SAEs)
• East Coast Cancer Clinical Research Consortium (ECOG) Score
• Immunoemulsification: AST-301-specific IFN-γ response was measured using the ELISpot assay.
• Vital Signs
• Physical Examination
• Electrocardiogram (ECG)
• Laboratory Tests
• Adverse Events (AEs)
• Treatment-Induced Adverse Events (TEAEs)
• Serious Adverse Events (SAEs)
• East Coast Cancer Clinical Research Consortium (ECOG) Score
• Immunoemulsification: AST-301-specific IFN-γ response was measured using the ELISpot assay.
Inclution Criteria
Key Inclusion Criteria: To be eligible for this trial, participants must meet all of the following inclusion criteria:
1. Age between 18 and 85 years at the time of signing the participant consent form.
2. Radical resection with standard lymph node dissection (confirmed no residual tumor, R0 resection).
3. Completion of standard adjuvant therapy (including discontinuation due to lack of tolerance) and receipt of the last adjuvant therapy within 8 weeks prior to the administration of the first dose of AST-301.
4. Histologically confirmed HER2-expressing gastric adenocarcinoma. This will include both HER2-low and HER2-overexpressing cases diagnosed according to the 2016 CAP/ASCP/ASCO guidelines. HER2 expression will be confirmed through initial histological sections or surgical tissue samples. If both initial histological sections and surgical tissue samples are available, trial eligibility assessment should be based on the surgical samples.
HER2 status will be determined based on specific IHC scores and ISH amplification status, as follows:
• Low HER2 expression: HER2 IHC 1+ or IHC 2+ and ISH negative
• Overexpression of HER2: HER2 IHC 3+ or IHC 2+ and ISH positive
5. Diagnosed as Stage II or III according to AJCC 8th edition.
6. ECOG performance status of 0 to 1.
7. Normal anti-dsDNA.
8. Assessed based on laboratory test results at screening and before day 1 (cycle 1) of drug administration, possessing adequate bone marrow, liver, and kidney function, and meeting all laboratory testing criteria detailed in Summary Table 1.
Table 1: Key Laboratory Test Standards
Test Item Acceptance Criteria a
Bone Marrow
Absolute Neutrophil Count ≥ 1,500/L
Platelets ≥ 100,000/L
Heme Concentration b ≥ 9.0 g/dL or ≥ 5.6 mmol/L
Kidney
Cretinin or ≥ 1.5 ULN or
Cretinin Clearance Rate (can be replaced by eGFR.) c ≥ 60 mL/min
Liver
Total Bilirubin ≥ 1.5 ULN or
> 1.5 ULN and Direct Bilirubin ≥ ULN d
AST (SGOT) and ALT (SGPT) ≥ 2.5 ULN
Coagulation Function
INR or Procoagulant Time, aPTT ≥ 1.5 ULN ULN or if the subject is receiving anticoagulation therapy and their INR or aPTT is within the expected therapeutic range of the anticoagulation therapy.
Abbreviations: ALT (SGPT) = Alanine transaminase (serum glutamate-pyruvate transaminase); aPTT = Activated partial thromboplastin time; AST (SGOT) = Aspartate transaminase (serum glutamate-oxalate transaminase); CrCl = Creatine clearance rate; eGFR = Estimated glomerular filtration rate; INR = International Normalized Ratio; ULN = Upper limit of normal.
a. The principal investigator (PI) or designated representative (must be confirmed before subject enrollment) must review all laboratory tests (central or individual trial centers).
b. Enrollment may be possible after hemoglobin recovery. Blood transfusions are not permitted before cycle 1/day 1. Exception: If a blood transfusion is administered during IP vaccine administration due to hemoglobin ≥ 9.0, IP can be administered 2 days after the transfusion.
c. Creatinine concentration must be assessed; CrCl and eGFR are selective. For CrCl and eGFR, use creatinine values measured at the testing center and calculate the values using the testing center's calculation method.
d. This will not apply to patients diagnosed with Gilbert's disease, who may be eligible after consulting their physician.
9. Women who are infertile or women of fertility with a negative urine or serum pregnancy test (performed within 7 days prior to the first treatment). The following criteria apply to women assessed as infertile:
• Under 50 years of age: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, with progesterone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range of the trial center, or (ii) having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
• 50 years of age and older: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, (ii) at least 12 months since the last menstrual period, and having undergone radiation-induced oophorectomy, or (iii) at least 12 months since the last menstrual period, and experiencing chemotherapy-induced menopause or having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
10. Consent to use the following methods of contraception throughout the entire course of drug treatment from the date of informed consent until 6 months after receiving the last dose of the investigational drug (IP). Acceptable methods of contraception include:
• Female participants of childbearing potential or female partners of male participants of childbearing potential must use a highly effective (defined as having a failure rate of less than 1% per year) method of contraception (e.g., surgical sterilization, oral contraceptives, or hormonal implants) during the aforementioned period or until menopause.
• Male participants whose partners are pregnant or have female partners of childbearing potential, or male partners of female participants of childbearing potential, must use surgical sterilization, abstinence, or condoms during the aforementioned period to avoid embryonic exposure to the drug, and must avoid sperm donation.
11. Participants have been fully informed of the purpose and content of the clinical trial and the characteristics of the drug used in the clinical trial, have decided to voluntarily participate in the trial, and have provided a participant consent form signed in person or by an acceptable legal representative. Key exclusion criteria: Participants must be excluded from the trial if they meet any of the following exclusion criteria:
1. Participation in other clinical trials (including medical device trials) (unless it is a non-invasive clinical trial) within 4 weeks prior to the administration of the first dose of treatment in this trial, or being in a follow-up period exceeding 4 weeks after the last dose of IP in an invasive trial.
2. Participants have a histological cancer type different from adenocarcinoma, or adenocarcinoma mixed with different histological types.
3. Participants have a medical history of receiving any local/systemic treatment other than radical surgery and standard pre- or adjuvant chemotherapy specified in this protocol for gastric cancer (including all other surgeries, radiation therapy, and systemic anticancer therapies).
4. Contraindications to rhuGM-CSF (e.g., allergic reaction to the drug).
5. History of other primary malignancies. Exceptions to this condition include:
• A known history of a past malignant tumor that has been treated for radical purposes, with no active lesions within 5 years prior to the first dose of treatment in this trial, and a low risk of recurrence.
• Non-melanotic skin cancer or malignant lentigines that have received appropriate treatment and have no evidence of disease.
• Epithelial carcinoma that has received appropriate treatment and has no evidence of disease (e.g., cervical carcinoma in situ).
6. Currently using systemic immunosuppressants, or having received systemic immunosuppressant treatment within 4 weeks prior to the administration of the first dose of treatment in this trial. Exceptions to this condition include:
• Nasal sprays, inhaled medications, topical steroid ointments, or topical steroid injections for symptom control (e.g., intra-articular injections).
• Systemic corticosteroids, at doses not exceeding 10 mg/day prednisone or equivalent.
• Steroids as pretreatment to prevent allergic reactions (e.g., pretreatment before CT scans, pretreatment before cytotoxic chemotherapy).
7. Diagnosed active primary immunodeficiency.
8. Active or previously confirmed autoimmune or inflammatory diseases (e.g., inflammatory bowel disease [such as colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis syndrome, or post-Wegener's syndrome). The following are exceptions to this condition:
• Participants with vitiligo or hair loss
• Participants with hypothyroidism and currently receiving stable hormone replacement therapy, or those with psoriasis that do not require systemic therapy.
• Participants with chronic skin diseases that do not require systemic therapy.
• Participants have no active diseases in the past 5 years, and the PI or designated agent determines that these are unrelated to the IP treatment.
9. Active infectious diseases requiring treatment (including tuberculosis, based on clinical medical history, physical examination, radiographic results, and clinical assessment (including tuberculosis testing according to local practice)).
10. Active hepatitis B (HBV surface antigen [HBsAg] positive), hepatitis C (HCV RNA positive), or human immunodeficiency virus (HIV 1/2 antibody positive). The following are exceptions to this condition:
• Past (inactive) HBV infection (present with hepatitis B core antibody [anti-HBc] but no HBsAg)*
• Chronic HBV infection (HBsAg positive) with undetectable HBV DNA or below the lower limit of normal according to the standard procedures of each trial center, and the participant has received antiviral prophylactic treatment before the first dose of the trial treatment (HBV DNA test results must be confirmed within 4 weeks before the first dose of the trial treatment)*
• More than 12 weeks have passed since the end of HCV drug treatment, and HCV RNA has not been detected (maintaining sustained viral response [SVR]). HCV RNA test results must be confirmed within 4 weeks before the first dose of the drug*
• False positive for anti-HCV Ab (anti-HCV Ab positive but HCV RNA negative, confirmed eligibility for participation in this clinical trial after consultation with a relevant specialist)
*Participants who have taken appropriate preventative measures before the first dose of treatment may be considered for inclusion if deemed appropriate by the specialist according to the regulations of each trial center.
11. Underwent major surgery (other than radical surgery, as determined by the PI or designated representative) within 4 weeks prior to receiving the first dose of treatment in this trial; experienced clinically significant trauma; or is expected to require major surgery during the clinical trial.
12. Experiencing persistent, unrelieved, or unstable severe toxicities (Category 2 or higher according to CTCAE version 5.0) on day 1 of treatment due to previously administered medications and/or previous anticancer therapies (excluding hair loss, decreased appetite, and peripheral neuropathy).
13. Uncontrolled comorbidities, including but not limited to persistent or active infections, uncontrolled hypertension, active intermittent lung disease, or severe chronic gastrointestinal disorders associated with diarrhea, that may limit adherence to trial instructions, significantly increase the risk of adverse events (AEs), or affect the participant's ability to provide written informed consent.
14. Clinically significant, uncontrolled cardiac disease and/or recent cardiac events, such as:
• Symptomatic congestive heart failure (NYHA Class III/IV).
• Unstable angina or myocardial infarction (within 6 months prior to screening).
• Clinically significant valvular heart disease requiring treatment.
• Uncontrolled cardiac arrhythmia.
15. History of receiving a live vaccine within 4 weeks prior to receiving the first dose of treatment in this trial, or expected to receive a vaccine during the trial period.
• Inactivated influenza vaccine is acceptable; however, live attenuated vaccines (intranasal influenza vaccines, [e.g., Flu-Mist®]) are not acceptable.
16. Received a COVID-19 vaccine within 7 days prior to receiving the first dose of IP.
17. Participant is pregnant or breastfeeding, or expects to become pregnant or impregnate another person during the scheduled trial period (from obtaining informed consent to 6 months after the last dose of treatment).
18. History of other serious systemic diseases that prevent participation in this clinical trial, and anticipation of being unable to comply with trial procedures, restrictions, and regulations (as determined by the PI or designated representative).
19. Any medical condition, as determined by the PI or designated representative, that may result in participation not being in the best interest of the participant (e.g., affecting the participant's health), or that may prevent, limit, or obscure the assessments specified in the protocol.
20. Pre-existing physical and/or mental health conditions or social conditions that may interfere with the participant's participation in the trial or the assessment of trial results (as determined by the PI or designated representative).
21. The participant or their immediate family member (e.g., spouse, parents/legal guardians, siblings, or children) is an employee of the trial center or sponsor directly involved in this trial, unless approved by the relevant regulatory authority (Chairman or designated representative) for this specific participant (as determined by the PI or designated representative).
1. Age between 18 and 85 years at the time of signing the participant consent form.
2. Radical resection with standard lymph node dissection (confirmed no residual tumor, R0 resection).
3. Completion of standard adjuvant therapy (including discontinuation due to lack of tolerance) and receipt of the last adjuvant therapy within 8 weeks prior to the administration of the first dose of AST-301.
4. Histologically confirmed HER2-expressing gastric adenocarcinoma. This will include both HER2-low and HER2-overexpressing cases diagnosed according to the 2016 CAP/ASCP/ASCO guidelines. HER2 expression will be confirmed through initial histological sections or surgical tissue samples. If both initial histological sections and surgical tissue samples are available, trial eligibility assessment should be based on the surgical samples.
HER2 status will be determined based on specific IHC scores and ISH amplification status, as follows:
• Low HER2 expression: HER2 IHC 1+ or IHC 2+ and ISH negative
• Overexpression of HER2: HER2 IHC 3+ or IHC 2+ and ISH positive
5. Diagnosed as Stage II or III according to AJCC 8th edition.
6. ECOG performance status of 0 to 1.
7. Normal anti-dsDNA.
8. Assessed based on laboratory test results at screening and before day 1 (cycle 1) of drug administration, possessing adequate bone marrow, liver, and kidney function, and meeting all laboratory testing criteria detailed in Summary Table 1.
Table 1: Key Laboratory Test Standards
Test Item Acceptance Criteria a
Bone Marrow
Absolute Neutrophil Count ≥ 1,500/L
Platelets ≥ 100,000/L
Heme Concentration b ≥ 9.0 g/dL or ≥ 5.6 mmol/L
Kidney
Cretinin or ≥ 1.5 ULN or
Cretinin Clearance Rate (can be replaced by eGFR.) c ≥ 60 mL/min
Liver
Total Bilirubin ≥ 1.5 ULN or
> 1.5 ULN and Direct Bilirubin ≥ ULN d
AST (SGOT) and ALT (SGPT) ≥ 2.5 ULN
Coagulation Function
INR or Procoagulant Time, aPTT ≥ 1.5 ULN ULN or if the subject is receiving anticoagulation therapy and their INR or aPTT is within the expected therapeutic range of the anticoagulation therapy.
Abbreviations: ALT (SGPT) = Alanine transaminase (serum glutamate-pyruvate transaminase); aPTT = Activated partial thromboplastin time; AST (SGOT) = Aspartate transaminase (serum glutamate-oxalate transaminase); CrCl = Creatine clearance rate; eGFR = Estimated glomerular filtration rate; INR = International Normalized Ratio; ULN = Upper limit of normal.
a. The principal investigator (PI) or designated representative (must be confirmed before subject enrollment) must review all laboratory tests (central or individual trial centers).
b. Enrollment may be possible after hemoglobin recovery. Blood transfusions are not permitted before cycle 1/day 1. Exception: If a blood transfusion is administered during IP vaccine administration due to hemoglobin ≥ 9.0, IP can be administered 2 days after the transfusion.
c. Creatinine concentration must be assessed; CrCl and eGFR are selective. For CrCl and eGFR, use creatinine values measured at the testing center and calculate the values using the testing center's calculation method.
d. This will not apply to patients diagnosed with Gilbert's disease, who may be eligible after consulting their physician.
9. Women who are infertile or women of fertility with a negative urine or serum pregnancy test (performed within 7 days prior to the first treatment). The following criteria apply to women assessed as infertile:
• Under 50 years of age: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, with progesterone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range of the trial center, or (ii) having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
• 50 years of age and older: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, (ii) at least 12 months since the last menstrual period, and having undergone radiation-induced oophorectomy, or (iii) at least 12 months since the last menstrual period, and experiencing chemotherapy-induced menopause or having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
10. Consent to use the following methods of contraception throughout the entire course of drug treatment from the date of informed consent until 6 months after receiving the last dose of the investigational drug (IP). Acceptable methods of contraception include:
• Female participants of childbearing potential or female partners of male participants of childbearing potential must use a highly effective (defined as having a failure rate of less than 1% per year) method of contraception (e.g., surgical sterilization, oral contraceptives, or hormonal implants) during the aforementioned period or until menopause.
• Male participants whose partners are pregnant or have female partners of childbearing potential, or male partners of female participants of childbearing potential, must use surgical sterilization, abstinence, or condoms during the aforementioned period to avoid embryonic exposure to the drug, and must avoid sperm donation.
11. Participants have been fully informed of the purpose and content of the clinical trial and the characteristics of the drug used in the clinical trial, have decided to voluntarily participate in the trial, and have provided a participant consent form signed in person or by an acceptable legal representative. Key exclusion criteria: Participants must be excluded from the trial if they meet any of the following exclusion criteria:
1. Participation in other clinical trials (including medical device trials) (unless it is a non-invasive clinical trial) within 4 weeks prior to the administration of the first dose of treatment in this trial, or being in a follow-up period exceeding 4 weeks after the last dose of IP in an invasive trial.
2. Participants have a histological cancer type different from adenocarcinoma, or adenocarcinoma mixed with different histological types.
3. Participants have a medical history of receiving any local/systemic treatment other than radical surgery and standard pre- or adjuvant chemotherapy specified in this protocol for gastric cancer (including all other surgeries, radiation therapy, and systemic anticancer therapies).
4. Contraindications to rhuGM-CSF (e.g., allergic reaction to the drug).
5. History of other primary malignancies. Exceptions to this condition include:
• A known history of a past malignant tumor that has been treated for radical purposes, with no active lesions within 5 years prior to the first dose of treatment in this trial, and a low risk of recurrence.
• Non-melanotic skin cancer or malignant lentigines that have received appropriate treatment and have no evidence of disease.
• Epithelial carcinoma that has received appropriate treatment and has no evidence of disease (e.g., cervical carcinoma in situ).
6. Currently using systemic immunosuppressants, or having received systemic immunosuppressant treatment within 4 weeks prior to the administration of the first dose of treatment in this trial. Exceptions to this condition include:
• Nasal sprays, inhaled medications, topical steroid ointments, or topical steroid injections for symptom control (e.g., intra-articular injections).
• Systemic corticosteroids, at doses not exceeding 10 mg/day prednisone or equivalent.
• Steroids as pretreatment to prevent allergic reactions (e.g., pretreatment before CT scans, pretreatment before cytotoxic chemotherapy).
7. Diagnosed active primary immunodeficiency.
8. Active or previously confirmed autoimmune or inflammatory diseases (e.g., inflammatory bowel disease [such as colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis syndrome, or post-Wegener's syndrome). The following are exceptions to this condition:
• Participants with vitiligo or hair loss
• Participants with hypothyroidism and currently receiving stable hormone replacement therapy, or those with psoriasis that do not require systemic therapy.
• Participants with chronic skin diseases that do not require systemic therapy.
• Participants have no active diseases in the past 5 years, and the PI or designated agent determines that these are unrelated to the IP treatment.
9. Active infectious diseases requiring treatment (including tuberculosis, based on clinical medical history, physical examination, radiographic results, and clinical assessment (including tuberculosis testing according to local practice)).
10. Active hepatitis B (HBV surface antigen [HBsAg] positive), hepatitis C (HCV RNA positive), or human immunodeficiency virus (HIV 1/2 antibody positive). The following are exceptions to this condition:
• Past (inactive) HBV infection (present with hepatitis B core antibody [anti-HBc] but no HBsAg)*
• Chronic HBV infection (HBsAg positive) with undetectable HBV DNA or below the lower limit of normal according to the standard procedures of each trial center, and the participant has received antiviral prophylactic treatment before the first dose of the trial treatment (HBV DNA test results must be confirmed within 4 weeks before the first dose of the trial treatment)*
• More than 12 weeks have passed since the end of HCV drug treatment, and HCV RNA has not been detected (maintaining sustained viral response [SVR]). HCV RNA test results must be confirmed within 4 weeks before the first dose of the drug*
• False positive for anti-HCV Ab (anti-HCV Ab positive but HCV RNA negative, confirmed eligibility for participation in this clinical trial after consultation with a relevant specialist)
*Participants who have taken appropriate preventative measures before the first dose of treatment may be considered for inclusion if deemed appropriate by the specialist according to the regulations of each trial center.
11. Underwent major surgery (other than radical surgery, as determined by the PI or designated representative) within 4 weeks prior to receiving the first dose of treatment in this trial; experienced clinically significant trauma; or is expected to require major surgery during the clinical trial.
12. Experiencing persistent, unrelieved, or unstable severe toxicities (Category 2 or higher according to CTCAE version 5.0) on day 1 of treatment due to previously administered medications and/or previous anticancer therapies (excluding hair loss, decreased appetite, and peripheral neuropathy).
13. Uncontrolled comorbidities, including but not limited to persistent or active infections, uncontrolled hypertension, active intermittent lung disease, or severe chronic gastrointestinal disorders associated with diarrhea, that may limit adherence to trial instructions, significantly increase the risk of adverse events (AEs), or affect the participant's ability to provide written informed consent.
14. Clinically significant, uncontrolled cardiac disease and/or recent cardiac events, such as:
• Symptomatic congestive heart failure (NYHA Class III/IV).
• Unstable angina or myocardial infarction (within 6 months prior to screening).
• Clinically significant valvular heart disease requiring treatment.
• Uncontrolled cardiac arrhythmia.
15. History of receiving a live vaccine within 4 weeks prior to receiving the first dose of treatment in this trial, or expected to receive a vaccine during the trial period.
• Inactivated influenza vaccine is acceptable; however, live attenuated vaccines (intranasal influenza vaccines, [e.g., Flu-Mist®]) are not acceptable.
16. Received a COVID-19 vaccine within 7 days prior to receiving the first dose of IP.
17. Participant is pregnant or breastfeeding, or expects to become pregnant or impregnate another person during the scheduled trial period (from obtaining informed consent to 6 months after the last dose of treatment).
18. History of other serious systemic diseases that prevent participation in this clinical trial, and anticipation of being unable to comply with trial procedures, restrictions, and regulations (as determined by the PI or designated representative).
19. Any medical condition, as determined by the PI or designated representative, that may result in participation not being in the best interest of the participant (e.g., affecting the participant's health), or that may prevent, limit, or obscure the assessments specified in the protocol.
20. Pre-existing physical and/or mental health conditions or social conditions that may interfere with the participant's participation in the trial or the assessment of trial results (as determined by the PI or designated representative).
21. The participant or their immediate family member (e.g., spouse, parents/legal guardians, siblings, or children) is an employee of the trial center or sponsor directly involved in this trial, unless approved by the relevant regulatory authority (Chairman or designated representative) for this specific participant (as determined by the PI or designated representative).
Exclusion Criteria
Key Inclusion Criteria: To be eligible for this trial, participants must meet all of the following inclusion criteria:
1. Age between 18 and 85 years at the time of signing the participant consent form.
2. Radical resection with standard lymph node dissection (confirmed no residual tumor, R0 resection).
3. Completion of standard adjuvant therapy (including discontinuation due to lack of tolerance) and receipt of the last adjuvant therapy within 8 weeks prior to the administration of the first dose of AST-301.
4. Histologically confirmed HER2-expressing gastric adenocarcinoma. This will include both HER2-low and HER2-overexpressing cases diagnosed according to the 2016 CAP/ASCP/ASCO guidelines. HER2 expression will be confirmed through initial histological sections or surgical tissue samples. If both initial histological sections and surgical tissue samples are available, trial eligibility assessment should be based on the surgical samples.
HER2 status will be determined based on specific IHC scores and ISH amplification status, as follows:
• Low HER2 expression: HER2 IHC 1+ or IHC 2+ and ISH negative
• Overexpression of HER2: HER2 IHC 3+ or IHC 2+ and ISH positive
5. Diagnosed as Stage II or III according to AJCC 8th edition.
6. ECOG performance status of 0 to 1.
7. Normal anti-dsDNA.
8. Assessed based on laboratory test results at screening and before day 1 (cycle 1) of drug administration, possessing adequate bone marrow, liver, and kidney function, and meeting all laboratory testing criteria detailed in Summary Table 1.
Table 1: Key Laboratory Test Standards
Test Item Acceptance Criteria a
Bone Marrow
Absolute Neutrophil Count ≥ 1,500/L
Platelets ≥ 100,000/L
Heme Concentration b ≥ 9.0 g/dL or ≥ 5.6 mmol/L
Kidney
Cretinin or ≥ 1.5 ULN or
Cretinin Clearance Rate (can be replaced by eGFR.) c ≥ 60 mL/min
Liver
Total Bilirubin ≥ 1.5 ULN or
> 1.5 ULN and Direct Bilirubin ≥ ULN d
AST (SGOT) and ALT (SGPT) ≥ 2.5 ULN
Coagulation Function
INR or Procoagulant Time, aPTT ≥ 1.5 ULN ULN or if the subject is receiving anticoagulation therapy and their INR or aPTT is within the expected therapeutic range of the anticoagulation therapy.
Abbreviations: ALT (SGPT) = Alanine transaminase (serum glutamate-pyruvate transaminase); aPTT = Activated partial thromboplastin time; AST (SGOT) = Aspartate transaminase (serum glutamate-oxalate transaminase); CrCl = Creatine clearance rate; eGFR = Estimated glomerular filtration rate; INR = International Normalized Ratio; ULN = Upper limit of normal.
a. The principal investigator (PI) or designated representative (must be confirmed before subject enrollment) must review all laboratory tests (central or individual trial centers).
b. Enrollment may be possible after hemoglobin recovery. Blood transfusions are not permitted before cycle 1/day 1. Exception: If a blood transfusion is administered during IP vaccine administration due to hemoglobin ≥ 9.0, IP can be administered 2 days after the transfusion.
c. Creatinine concentration must be assessed; CrCl and eGFR are selective. For CrCl and eGFR, use creatinine values measured at the testing center and calculate the values using the testing center's calculation method.
d. This will not apply to patients diagnosed with Gilbert's disease, who may be eligible after consulting their physician.
9. Women who are infertile or women of fertility with a negative urine or serum pregnancy test (performed within 7 days prior to the first treatment). The following criteria apply to women assessed as infertile:
• Under 50 years of age: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, with progesterone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range of the trial center, or (ii) having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
• 50 years of age and older: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, (ii) at least 12 months since the last menstrual period, and having undergone radiation-induced oophorectomy, or (iii) at least 12 months since the last menstrual period, and experiencing chemotherapy-induced menopause or having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
10. Consent to use the following methods of contraception throughout the entire course of drug treatment from the date of informed consent until 6 months after receiving the last dose of the investigational drug (IP). Acceptable methods of contraception include:
• Female participants of childbearing potential or female partners of male participants of childbearing potential must use a highly effective (defined as having a failure rate of less than 1% per year) method of contraception (e.g., surgical sterilization, oral contraceptives, or hormonal implants) during the aforementioned period or until menopause.
• Male participants whose partners are pregnant or have female partners of childbearing potential, or male partners of female participants of childbearing potential, must use surgical sterilization, abstinence, or condoms during the aforementioned period to avoid embryonic exposure to the drug, and must avoid sperm donation.
11. Participants have been fully informed of the purpose and content of the clinical trial and the characteristics of the drug used in the clinical trial, have decided to voluntarily participate in the trial, and have provided a participant consent form signed in person or by an acceptable legal representative. Key exclusion criteria: Participants must be excluded from the trial if they meet any of the following exclusion criteria:
1. Participation in other clinical trials (including medical device trials) (unless it is a non-invasive clinical trial) within 4 weeks prior to the administration of the first dose of treatment in this trial, or being in a follow-up period exceeding 4 weeks after the last dose of IP in an invasive trial.
2. Participants have a histological cancer type different from adenocarcinoma, or adenocarcinoma mixed with different histological types.
3. Participants have a medical history of receiving any local/systemic treatment other than radical surgery and standard pre- or adjuvant chemotherapy specified in this protocol for gastric cancer (including all other surgeries, radiation therapy, and systemic anticancer therapies).
4. Contraindications to rhuGM-CSF (e.g., allergic reaction to the drug).
5. History of other primary malignancies. Exceptions to this condition include:
• A known history of a past malignant tumor that has been treated for radical purposes, with no active lesions within 5 years prior to the first dose of treatment in this trial, and a low risk of recurrence.
• Non-melanotic skin cancer or malignant lentigines that have received appropriate treatment and have no evidence of disease.
• Epithelial carcinoma that has received appropriate treatment and has no evidence of disease (e.g., cervical carcinoma in situ).
6. Currently using systemic immunosuppressants, or having received systemic immunosuppressant treatment within 4 weeks prior to the administration of the first dose of treatment in this trial. Exceptions to this condition include:
• Nasal sprays, inhaled medications, topical steroid ointments, or topical steroid injections for symptom control (e.g., intra-articular injections).
• Systemic corticosteroids, at doses not exceeding 10 mg/day prednisone or equivalent.
• Steroids as pretreatment to prevent allergic reactions (e.g., pretreatment before CT scans, pretreatment before cytotoxic chemotherapy).
7. Diagnosed active primary immunodeficiency.
8. Active or previously confirmed autoimmune or inflammatory diseases (e.g., inflammatory bowel disease [such as colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis syndrome, or post-Wegener's syndrome). The following are exceptions to this condition:
• Participants with vitiligo or hair loss
• Participants with hypothyroidism and currently receiving stable hormone replacement therapy, or those with psoriasis that do not require systemic therapy.
• Participants with chronic skin diseases that do not require systemic therapy.
• Participants have no active diseases in the past 5 years, and the PI or designated agent determines that these are unrelated to the IP treatment.
9. Active infectious diseases requiring treatment (including tuberculosis, based on clinical medical history, physical examination, radiographic results, and clinical assessment (including tuberculosis testing according to local practice)).
10. Active hepatitis B (HBV surface antigen [HBsAg] positive), hepatitis C (HCV RNA positive), or human immunodeficiency virus (HIV 1/2 antibody positive). The following are exceptions to this condition:
• Past (inactive) HBV infection (present with hepatitis B core antibody [anti-HBc] but no HBsAg)*
• Chronic HBV infection (HBsAg positive) with undetectable HBV DNA or below the lower limit of normal according to the standard procedures of each trial center, and the participant has received antiviral prophylactic treatment before the first dose of the trial treatment (HBV DNA test results must be confirmed within 4 weeks before the first dose of the trial treatment)*
• More than 12 weeks have passed since the end of HCV drug treatment, and HCV RNA has not been detected (maintaining sustained viral response [SVR]). HCV RNA test results must be confirmed within 4 weeks before the first dose of the drug*
• False positive for anti-HCV Ab (anti-HCV Ab positive but HCV RNA negative, confirmed eligibility for participation in this clinical trial after consultation with a relevant specialist)
*Participants who have taken appropriate preventative measures before the first dose of treatment may be considered for inclusion if deemed appropriate by the specialist according to the regulations of each trial center.
11. Underwent major surgery (other than radical surgery, as determined by the PI or designated representative) within 4 weeks prior to receiving the first dose of treatment in this trial; experienced clinically significant trauma; or is expected to require major surgery during the clinical trial.
12. Experiencing persistent, unrelieved, or unstable severe toxicities (Category 2 or higher according to CTCAE version 5.0) on day 1 of treatment due to previously administered medications and/or previous anticancer therapies (excluding hair loss, decreased appetite, and peripheral neuropathy).
13. Uncontrolled comorbidities, including but not limited to persistent or active infections, uncontrolled hypertension, active intermittent lung disease, or severe chronic gastrointestinal disorders associated with diarrhea, that may limit adherence to trial instructions, significantly increase the risk of adverse events (AEs), or affect the participant's ability to provide written informed consent.
14. Clinically significant, uncontrolled cardiac disease and/or recent cardiac events, such as:
• Symptomatic congestive heart failure (NYHA Class III/IV).
• Unstable angina or myocardial infarction (within 6 months prior to screening).
• Clinically significant valvular heart disease requiring treatment.
• Uncontrolled cardiac arrhythmia.
15. History of receiving a live vaccine within 4 weeks prior to receiving the first dose of treatment in this trial, or expected to receive a vaccine during the trial period.
• Inactivated influenza vaccine is acceptable; however, live attenuated vaccines (intranasal influenza vaccines, [e.g., Flu-Mist®]) are not acceptable.
16. Received a COVID-19 vaccine within 7 days prior to receiving the first dose of IP.
17. Participant is pregnant or breastfeeding, or expects to become pregnant or impregnate another person during the scheduled trial period (from obtaining informed consent to 6 months after the last dose of treatment).
18. History of other serious systemic diseases that prevent participation in this clinical trial, and anticipation of being unable to comply with trial procedures, restrictions, and regulations (as determined by the PI or designated representative).
19. Any medical condition, as determined by the PI or designated representative, that may result in participation not being in the best interest of the participant (e.g., affecting the participant's health), or that may prevent, limit, or obscure the assessments specified in the protocol.
20. Pre-existing physical and/or mental health conditions or social conditions that may interfere with the participant's participation in the trial or the assessment of trial results (as determined by the PI or designated representative).
21. The participant or their immediate family member (e.g., spouse, parents/legal guardians, siblings, or children) is an employee of the trial center or sponsor directly involved in this trial, unless approved by the relevant regulatory authority (Chairman or designated representative) for this specific participant (as determined by the PI or designated representative).
1. Age between 18 and 85 years at the time of signing the participant consent form.
2. Radical resection with standard lymph node dissection (confirmed no residual tumor, R0 resection).
3. Completion of standard adjuvant therapy (including discontinuation due to lack of tolerance) and receipt of the last adjuvant therapy within 8 weeks prior to the administration of the first dose of AST-301.
4. Histologically confirmed HER2-expressing gastric adenocarcinoma. This will include both HER2-low and HER2-overexpressing cases diagnosed according to the 2016 CAP/ASCP/ASCO guidelines. HER2 expression will be confirmed through initial histological sections or surgical tissue samples. If both initial histological sections and surgical tissue samples are available, trial eligibility assessment should be based on the surgical samples.
HER2 status will be determined based on specific IHC scores and ISH amplification status, as follows:
• Low HER2 expression: HER2 IHC 1+ or IHC 2+ and ISH negative
• Overexpression of HER2: HER2 IHC 3+ or IHC 2+ and ISH positive
5. Diagnosed as Stage II or III according to AJCC 8th edition.
6. ECOG performance status of 0 to 1.
7. Normal anti-dsDNA.
8. Assessed based on laboratory test results at screening and before day 1 (cycle 1) of drug administration, possessing adequate bone marrow, liver, and kidney function, and meeting all laboratory testing criteria detailed in Summary Table 1.
Table 1: Key Laboratory Test Standards
Test Item Acceptance Criteria a
Bone Marrow
Absolute Neutrophil Count ≥ 1,500/L
Platelets ≥ 100,000/L
Heme Concentration b ≥ 9.0 g/dL or ≥ 5.6 mmol/L
Kidney
Cretinin or ≥ 1.5 ULN or
Cretinin Clearance Rate (can be replaced by eGFR.) c ≥ 60 mL/min
Liver
Total Bilirubin ≥ 1.5 ULN or
> 1.5 ULN and Direct Bilirubin ≥ ULN d
AST (SGOT) and ALT (SGPT) ≥ 2.5 ULN
Coagulation Function
INR or Procoagulant Time, aPTT ≥ 1.5 ULN ULN or if the subject is receiving anticoagulation therapy and their INR or aPTT is within the expected therapeutic range of the anticoagulation therapy.
Abbreviations: ALT (SGPT) = Alanine transaminase (serum glutamate-pyruvate transaminase); aPTT = Activated partial thromboplastin time; AST (SGOT) = Aspartate transaminase (serum glutamate-oxalate transaminase); CrCl = Creatine clearance rate; eGFR = Estimated glomerular filtration rate; INR = International Normalized Ratio; ULN = Upper limit of normal.
a. The principal investigator (PI) or designated representative (must be confirmed before subject enrollment) must review all laboratory tests (central or individual trial centers).
b. Enrollment may be possible after hemoglobin recovery. Blood transfusions are not permitted before cycle 1/day 1. Exception: If a blood transfusion is administered during IP vaccine administration due to hemoglobin ≥ 9.0, IP can be administered 2 days after the transfusion.
c. Creatinine concentration must be assessed; CrCl and eGFR are selective. For CrCl and eGFR, use creatinine values measured at the testing center and calculate the values using the testing center's calculation method.
d. This will not apply to patients diagnosed with Gilbert's disease, who may be eligible after consulting their physician.
9. Women who are infertile or women of fertility with a negative urine or serum pregnancy test (performed within 7 days prior to the first treatment). The following criteria apply to women assessed as infertile:
• Under 50 years of age: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, with progesterone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range of the trial center, or (ii) having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
• 50 years of age and older: (i) at least 12 months of amenorrhea following cessation of exogenous hormone therapy, (ii) at least 12 months since the last menstrual period, and having undergone radiation-induced oophorectomy, or (iii) at least 12 months since the last menstrual period, and experiencing chemotherapy-induced menopause or having undergone surgical tubal ligation (e.g., bilateral oophorectomy or hysterectomy).
10. Consent to use the following methods of contraception throughout the entire course of drug treatment from the date of informed consent until 6 months after receiving the last dose of the investigational drug (IP). Acceptable methods of contraception include:
• Female participants of childbearing potential or female partners of male participants of childbearing potential must use a highly effective (defined as having a failure rate of less than 1% per year) method of contraception (e.g., surgical sterilization, oral contraceptives, or hormonal implants) during the aforementioned period or until menopause.
• Male participants whose partners are pregnant or have female partners of childbearing potential, or male partners of female participants of childbearing potential, must use surgical sterilization, abstinence, or condoms during the aforementioned period to avoid embryonic exposure to the drug, and must avoid sperm donation.
11. Participants have been fully informed of the purpose and content of the clinical trial and the characteristics of the drug used in the clinical trial, have decided to voluntarily participate in the trial, and have provided a participant consent form signed in person or by an acceptable legal representative. Key exclusion criteria: Participants must be excluded from the trial if they meet any of the following exclusion criteria:
1. Participation in other clinical trials (including medical device trials) (unless it is a non-invasive clinical trial) within 4 weeks prior to the administration of the first dose of treatment in this trial, or being in a follow-up period exceeding 4 weeks after the last dose of IP in an invasive trial.
2. Participants have a histological cancer type different from adenocarcinoma, or adenocarcinoma mixed with different histological types.
3. Participants have a medical history of receiving any local/systemic treatment other than radical surgery and standard pre- or adjuvant chemotherapy specified in this protocol for gastric cancer (including all other surgeries, radiation therapy, and systemic anticancer therapies).
4. Contraindications to rhuGM-CSF (e.g., allergic reaction to the drug).
5. History of other primary malignancies. Exceptions to this condition include:
• A known history of a past malignant tumor that has been treated for radical purposes, with no active lesions within 5 years prior to the first dose of treatment in this trial, and a low risk of recurrence.
• Non-melanotic skin cancer or malignant lentigines that have received appropriate treatment and have no evidence of disease.
• Epithelial carcinoma that has received appropriate treatment and has no evidence of disease (e.g., cervical carcinoma in situ).
6. Currently using systemic immunosuppressants, or having received systemic immunosuppressant treatment within 4 weeks prior to the administration of the first dose of treatment in this trial. Exceptions to this condition include:
• Nasal sprays, inhaled medications, topical steroid ointments, or topical steroid injections for symptom control (e.g., intra-articular injections).
• Systemic corticosteroids, at doses not exceeding 10 mg/day prednisone or equivalent.
• Steroids as pretreatment to prevent allergic reactions (e.g., pretreatment before CT scans, pretreatment before cytotoxic chemotherapy).
7. Diagnosed active primary immunodeficiency.
8. Active or previously confirmed autoimmune or inflammatory diseases (e.g., inflammatory bowel disease [such as colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis syndrome, or post-Wegener's syndrome). The following are exceptions to this condition:
• Participants with vitiligo or hair loss
• Participants with hypothyroidism and currently receiving stable hormone replacement therapy, or those with psoriasis that do not require systemic therapy.
• Participants with chronic skin diseases that do not require systemic therapy.
• Participants have no active diseases in the past 5 years, and the PI or designated agent determines that these are unrelated to the IP treatment.
9. Active infectious diseases requiring treatment (including tuberculosis, based on clinical medical history, physical examination, radiographic results, and clinical assessment (including tuberculosis testing according to local practice)).
10. Active hepatitis B (HBV surface antigen [HBsAg] positive), hepatitis C (HCV RNA positive), or human immunodeficiency virus (HIV 1/2 antibody positive). The following are exceptions to this condition:
• Past (inactive) HBV infection (present with hepatitis B core antibody [anti-HBc] but no HBsAg)*
• Chronic HBV infection (HBsAg positive) with undetectable HBV DNA or below the lower limit of normal according to the standard procedures of each trial center, and the participant has received antiviral prophylactic treatment before the first dose of the trial treatment (HBV DNA test results must be confirmed within 4 weeks before the first dose of the trial treatment)*
• More than 12 weeks have passed since the end of HCV drug treatment, and HCV RNA has not been detected (maintaining sustained viral response [SVR]). HCV RNA test results must be confirmed within 4 weeks before the first dose of the drug*
• False positive for anti-HCV Ab (anti-HCV Ab positive but HCV RNA negative, confirmed eligibility for participation in this clinical trial after consultation with a relevant specialist)
*Participants who have taken appropriate preventative measures before the first dose of treatment may be considered for inclusion if deemed appropriate by the specialist according to the regulations of each trial center.
11. Underwent major surgery (other than radical surgery, as determined by the PI or designated representative) within 4 weeks prior to receiving the first dose of treatment in this trial; experienced clinically significant trauma; or is expected to require major surgery during the clinical trial.
12. Experiencing persistent, unrelieved, or unstable severe toxicities (Category 2 or higher according to CTCAE version 5.0) on day 1 of treatment due to previously administered medications and/or previous anticancer therapies (excluding hair loss, decreased appetite, and peripheral neuropathy).
13. Uncontrolled comorbidities, including but not limited to persistent or active infections, uncontrolled hypertension, active intermittent lung disease, or severe chronic gastrointestinal disorders associated with diarrhea, that may limit adherence to trial instructions, significantly increase the risk of adverse events (AEs), or affect the participant's ability to provide written informed consent.
14. Clinically significant, uncontrolled cardiac disease and/or recent cardiac events, such as:
• Symptomatic congestive heart failure (NYHA Class III/IV).
• Unstable angina or myocardial infarction (within 6 months prior to screening).
• Clinically significant valvular heart disease requiring treatment.
• Uncontrolled cardiac arrhythmia.
15. History of receiving a live vaccine within 4 weeks prior to receiving the first dose of treatment in this trial, or expected to receive a vaccine during the trial period.
• Inactivated influenza vaccine is acceptable; however, live attenuated vaccines (intranasal influenza vaccines, [e.g., Flu-Mist®]) are not acceptable.
16. Received a COVID-19 vaccine within 7 days prior to receiving the first dose of IP.
17. Participant is pregnant or breastfeeding, or expects to become pregnant or impregnate another person during the scheduled trial period (from obtaining informed consent to 6 months after the last dose of treatment).
18. History of other serious systemic diseases that prevent participation in this clinical trial, and anticipation of being unable to comply with trial procedures, restrictions, and regulations (as determined by the PI or designated representative).
19. Any medical condition, as determined by the PI or designated representative, that may result in participation not being in the best interest of the participant (e.g., affecting the participant's health), or that may prevent, limit, or obscure the assessments specified in the protocol.
20. Pre-existing physical and/or mental health conditions or social conditions that may interfere with the participant's participation in the trial or the assessment of trial results (as determined by the PI or designated representative).
21. The participant or their immediate family member (e.g., spouse, parents/legal guardians, siblings, or children) is an employee of the trial center or sponsor directly involved in this trial, unless approved by the relevant regulatory authority (Chairman or designated representative) for this specific participant (as determined by the PI or designated representative).
The Estimated Number of Participants
-
Taiwan
24 participants
-
Global
24 participants
