Clinical Trials List
Protocol NumberGBP-11-201
NCT Number(ClinicalTrials.gov Identfier)NCT02531854
2019-06-01 - 2022-12-31
Phase II
Terminated9
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A PHASE 2, OPEN-LABEL, RANDOMIZED, PARALLEL GROUP, CONTROLLED STUDY OF PEMETREXED MAINTENANCE WITH OR WITHOUT ADXS11-001 IMMUNOTHERAPY IN SUBJECTS WITH HUMAN PAPILLOMAVIRUS-POSITIVE, NON-SQUAMOUS, NONSMALL CELL LUNG CARCINOMA FOLLOWING FIRST-LINE INDUCTION CHEMOTHERAPY
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Trial Applicant
PROTECH PHARMASERVICES CORPORATION
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Sponsor
Global BioPharma.
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Trial scale
Taiwan Multiple Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chia-Lun Chang Division of Hematology & Oncology
- Han-Lin Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 吳美翰 Division of Radiology
- Jen-Fu Shih Division of Infectious Disease
- Heng-Sheng Chao Division of Thoracic Medicine
- Chao-Hua Chiu Division of Hematology & Oncology
- Yung-Hung Luo Division of Hematology & Oncology
- 蕭逸函 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Cheng-Ta Yang Division of Hematology & Oncology
- 林定佑 Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
- 謝任富 Division of Radiology
- 枋岳甫 Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chih-Cheng Chang Division of Thoracic Medicine
- Po-Hao Feng Division of Thoracic Medicine
- 徐惠玲 Division of Radiology
- Tzu-Tao Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
CRO
Co-Principal Investigator
- Gong-Yau Lan Division of Radiology
- 夏和雄 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chih-Yen Tu Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
LUNG CARCINOMA
Objectives
Primary:
The primary objective is to determine the progression-free survival (PFS) of pemetrexed plus ADXS11-001(also
known as axalimogene filolisbac/AXAL), versus pemetrexed alone, when administered as maintenance therapy
to subjects with HPV+, non-squamous, NSCLC who have had a documented partial response (PR) or stable
disease (SD) following first -line induction chemotherapy with a platinum-containing regimen.
Secondary:
1. To determine additional measures of antineoplastic effect in this subject population, including:
• Overall response rate (ORR)
• Duration of response (DR) or disease stabilization (SD)
• Overall survival(OS)
2. To evaluate the safety and tolerability of ADXS11-001 in combination with pemetrexed in this subject population
Test Drug
ADXS11-001
Active Ingredient
ADXS11-001
Dosage Form
Solution for Injection
Dosage
Each vial containing 5.5 mL at 2 mg/mL 1 × 10^9
Endpoints
1. Primary endpoint:
Progression-free survival (PFS) at the end of study
2. Secondary endpoints:
Adverse events; physical examinations, vital sign measurements; clinical laboratory evaluations; Lm surveillance
blood cultures
Proportion of patients who are alive and progression free at 12 months, Objective response rate (ORR), overall
survival (OS)
Progression-free survival (PFS) at the end of study
2. Secondary endpoints:
Adverse events; physical examinations, vital sign measurements; clinical laboratory evaluations; Lm surveillance
blood cultures
Proportion of patients who are alive and progression free at 12 months, Objective response rate (ORR), overall
survival (OS)
Inclution Criteria
1. Subjects at least 20 years of age on the day of signing informed consent
2. Subject has histologically-confirmed, metastatic, HPV+, non-squamous, NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma, or not otherwise specified [NOS; excluding those with biopsy samples containing a significant proportion of apparent squamous -type cells])
3. Subject has a documented response PR or SD following completion of 4 to 6 cycles of first-line induction chemotherapy with a standard platinum-containing doublet regimen, including those containing pemetrexed.
Note: Subjects with an activating/sensitizing EGFR mutation who have either failed or responded and relapsed following prior first-line therapy with a tyrosine kinase inhibitor (TKI) will be eligible for this study after achievement of an PR or SD with standard platinum- containing chemotherapy, as described above.
4. Subject has measurable and/or evaluable disease for response assessment per RECIST 1.1. Tumors within a previously irradiated field will be designated as “non -target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
5. Subject has adequate organ function
6. Subject has ECOG performance status (PS) 0-1 and an anticipated life expectancy of > 6 months at study enrollment
7. Subject has resolved acute effects of any prior therapy to baseline severity of Grade <2 per NCI CTCAE except for AEs not constituting a safety risk by investigator judgment.
8. Women of childbearing potential (WOCBP) with a negative urine pregnancy test at Screening.
9. WOCBP must agree to ongoing use 2 methods of study doctor approved birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study from Screening through 120 days after the last dose of study medication.
10. Subject is able to provide written informed consent.
2. Subject has histologically-confirmed, metastatic, HPV+, non-squamous, NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma, or not otherwise specified [NOS; excluding those with biopsy samples containing a significant proportion of apparent squamous -type cells])
3. Subject has a documented response PR or SD following completion of 4 to 6 cycles of first-line induction chemotherapy with a standard platinum-containing doublet regimen, including those containing pemetrexed.
Note: Subjects with an activating/sensitizing EGFR mutation who have either failed or responded and relapsed following prior first-line therapy with a tyrosine kinase inhibitor (TKI) will be eligible for this study after achievement of an PR or SD with standard platinum- containing chemotherapy, as described above.
4. Subject has measurable and/or evaluable disease for response assessment per RECIST 1.1. Tumors within a previously irradiated field will be designated as “non -target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
5. Subject has adequate organ function
6. Subject has ECOG performance status (PS) 0-1 and an anticipated life expectancy of > 6 months at study enrollment
7. Subject has resolved acute effects of any prior therapy to baseline severity of Grade <2 per NCI CTCAE except for AEs not constituting a safety risk by investigator judgment.
8. Women of childbearing potential (WOCBP) with a negative urine pregnancy test at Screening.
9. WOCBP must agree to ongoing use 2 methods of study doctor approved birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study from Screening through 120 days after the last dose of study medication.
10. Subject is able to provide written informed consent.
Exclusion Criteria
1. In the opinion of the investigator, subject has rapidly progressing disease, OR has life expectancy of less than 6 months, OR would be unable to receive at least 1 cycle of therapy.
2. Subject has received chemotherapy and/or radiation therapy within ≤2 weeks of study treatment.
Note: Prior radiotherapy aimed at local palliation or attempted local disease control is permitted. Subjects requiring radiation therapy for pain management will have study treatment discontinued or interrupted, at the Investigator’s discretion and following discussion with the Sponsor's Medical Monitor(s), in order to allow for appropriate management.
3. Subject has not recovered (i.e., Grade ≤1 at baseline) from AEs, with the exception of alopecia due to previously administered agent(s).
4. Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
5. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study.
6. Has neuropathy (sensory and motor) ≥Grade 3 per NCI CTCAE v 4.03.
7. Subject has diagnosis of immunodeficiency, is dependent on or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 day s prior to the first dose of trial treatment with the exception of topical corticosteroids and occasional inhaled corticosteroids, as indicated.
8. Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
9. Subject has concurrent unstable or uncontrolled medical condition (e.g., active uncontrolled systemic infection, poorly controlled hypertension or history of poor compliance with an anti-hypertensive regimen, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the Investigator, could compromise the subject or the study.
10. Subject is pregnant or breastfeeding, or expecting to conceive a child/children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
11. Subject is currently participating in or has participated in a study of an investigational agent(s) or using an investigational device within 4 weeks of the first dose of trial treatment.
12. Subject has active infection requiring systemic therapy or is dependent on or currently receiving antibiotics that cannot be discontinued before dosing. (Note: Subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any ADXS11-001 infusion).
13. Subject has a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial.
14. Subject has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g., Port -a- Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.
15. Subjects who are receiving or may receive future treatment with PI3K or TNFα inhibitors.
16. Subject with a contraindication (e.g., sensitivity/allergy) to trimethoprim/ sulfamethoxazole and ampicillin.
17. Subject with any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could place the subject at higher risk derived from his /her participation in the study, could confound results of the study, or would be likely to prevent the subject from complying with the requirements of the study or completing the study.
18. Subject has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
19. Subject has a known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected).
20. Subject has received a live vaccine within 28 days prior to the first dose of trial treatment.
21. Has undergone a major surgery, including surgery for a new artificial implant and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment. NOTE: All toxicities and/or complications must have recovered to baseline or Grade 1 prior to the initiation of ADXS11-001 study therapy. Sponsor must be consulted prior to enrolling subjects on the study who recently had a major surgery or have new artificial implant, and/or devices.
22. Subject has a known allergy to any component of the study treatments.
23. Subject has a history of listeriosis or prior ADXS11-001 therapy.
24. Subject has more than 1 prior anti-cancer chemotherapeutic regimen for the underlying malignancy, except subjects with NSCLC with activating/sensitizing EGFR mutations who may have received additional prior therapy.
o Note: For subjects who received post-operative adjuvant chemotherapy, it will be accepted if the last dose of the adjuvant therapy prior to the first-line induction chemotherapy is ≥1 year. It will be accepted if the last dose of the adjuvant therapy prior to the first -line induction chemotherapy is <1 year but use pemetrexed-based chemotherapy. Subjects will not be enrolled in the study if the last dose of the adjuvant therapy prior to the first-line induction chemotherapy is <1 year and did not use pemetrexed-based chemotherapy as adjuvant therapy.
25. Subject had prior induction chemotherapy with a regimen containing bevacizumab (continued standard of care maintenance therapy with bevacizumab will not be allowed )
26. Subject had prior vaccines (with the exception of influenza vaccine, pneumococcal vaccine, and varicella zoster vaccine), within 28 days prior to study treatment and during study
27. Herbal preparations, or related non-prescription preparations/supplements containing herbal ingredients, aimed at treating the underlying malignancy within 2 weeks prior to study treatment and during study
28. Chronic use of immunosuppressant drugs and/or systemic corticosteroids, or any other form of immunosuppressive therapy within 1 week prior to study drug treatment. The following therapies are allowed:
o Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
o Oral replacement glucocorticoid therapy for adrenal insufficiency
o Low-dose maintenance steroid therapy (e.g., <10 mg prednisone/day) for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
o Local steroid injections
o Pre medication as prophylaxis for or treatment of immune-related AEs associated with study treatment
29. Other systemic hormonal therapy within 1 week prior to study treatment and during study. The following therapies are allowed:
o Hormonal therapy for non-cancer-related conditions (e.g., Megace for appetite stimulation, insulin for diabetes, hormone replacement therapy)
o Hormonal contraceptive therapy (in WOCBP must be combined with non-hormonal contraceptive equivalent to a double-barrier method)
30. Any other investigational treatments during study. This includes participation in any medical device or therapeutic intervention clinical trial.
31. Prophylactic use of hematopoietic growth factors within 1 week prior to study treatment and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated.
2. Subject has received chemotherapy and/or radiation therapy within ≤2 weeks of study treatment.
Note: Prior radiotherapy aimed at local palliation or attempted local disease control is permitted. Subjects requiring radiation therapy for pain management will have study treatment discontinued or interrupted, at the Investigator’s discretion and following discussion with the Sponsor's Medical Monitor(s), in order to allow for appropriate management.
3. Subject has not recovered (i.e., Grade ≤1 at baseline) from AEs, with the exception of alopecia due to previously administered agent(s).
4. Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
5. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study.
6. Has neuropathy (sensory and motor) ≥Grade 3 per NCI CTCAE v 4.03.
7. Subject has diagnosis of immunodeficiency, is dependent on or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 day s prior to the first dose of trial treatment with the exception of topical corticosteroids and occasional inhaled corticosteroids, as indicated.
8. Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
9. Subject has concurrent unstable or uncontrolled medical condition (e.g., active uncontrolled systemic infection, poorly controlled hypertension or history of poor compliance with an anti-hypertensive regimen, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the Investigator, could compromise the subject or the study.
10. Subject is pregnant or breastfeeding, or expecting to conceive a child/children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
11. Subject is currently participating in or has participated in a study of an investigational agent(s) or using an investigational device within 4 weeks of the first dose of trial treatment.
12. Subject has active infection requiring systemic therapy or is dependent on or currently receiving antibiotics that cannot be discontinued before dosing. (Note: Subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any ADXS11-001 infusion).
13. Subject has a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial.
14. Subject has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g., Port -a- Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.
15. Subjects who are receiving or may receive future treatment with PI3K or TNFα inhibitors.
16. Subject with a contraindication (e.g., sensitivity/allergy) to trimethoprim/ sulfamethoxazole and ampicillin.
17. Subject with any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could place the subject at higher risk derived from his /her participation in the study, could confound results of the study, or would be likely to prevent the subject from complying with the requirements of the study or completing the study.
18. Subject has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
19. Subject has a known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected).
20. Subject has received a live vaccine within 28 days prior to the first dose of trial treatment.
21. Has undergone a major surgery, including surgery for a new artificial implant and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment. NOTE: All toxicities and/or complications must have recovered to baseline or Grade 1 prior to the initiation of ADXS11-001 study therapy. Sponsor must be consulted prior to enrolling subjects on the study who recently had a major surgery or have new artificial implant, and/or devices.
22. Subject has a known allergy to any component of the study treatments.
23. Subject has a history of listeriosis or prior ADXS11-001 therapy.
24. Subject has more than 1 prior anti-cancer chemotherapeutic regimen for the underlying malignancy, except subjects with NSCLC with activating/sensitizing EGFR mutations who may have received additional prior therapy.
o Note: For subjects who received post-operative adjuvant chemotherapy, it will be accepted if the last dose of the adjuvant therapy prior to the first-line induction chemotherapy is ≥1 year. It will be accepted if the last dose of the adjuvant therapy prior to the first -line induction chemotherapy is <1 year but use pemetrexed-based chemotherapy. Subjects will not be enrolled in the study if the last dose of the adjuvant therapy prior to the first-line induction chemotherapy is <1 year and did not use pemetrexed-based chemotherapy as adjuvant therapy.
25. Subject had prior induction chemotherapy with a regimen containing bevacizumab (continued standard of care maintenance therapy with bevacizumab will not be allowed )
26. Subject had prior vaccines (with the exception of influenza vaccine, pneumococcal vaccine, and varicella zoster vaccine), within 28 days prior to study treatment and during study
27. Herbal preparations, or related non-prescription preparations/supplements containing herbal ingredients, aimed at treating the underlying malignancy within 2 weeks prior to study treatment and during study
28. Chronic use of immunosuppressant drugs and/or systemic corticosteroids, or any other form of immunosuppressive therapy within 1 week prior to study drug treatment. The following therapies are allowed:
o Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
o Oral replacement glucocorticoid therapy for adrenal insufficiency
o Low-dose maintenance steroid therapy (e.g., <10 mg prednisone/day) for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
o Local steroid injections
o Pre medication as prophylaxis for or treatment of immune-related AEs associated with study treatment
29. Other systemic hormonal therapy within 1 week prior to study treatment and during study. The following therapies are allowed:
o Hormonal therapy for non-cancer-related conditions (e.g., Megace for appetite stimulation, insulin for diabetes, hormone replacement therapy)
o Hormonal contraceptive therapy (in WOCBP must be combined with non-hormonal contraceptive equivalent to a double-barrier method)
30. Any other investigational treatments during study. This includes participation in any medical device or therapeutic intervention clinical trial.
31. Prophylactic use of hematopoietic growth factors within 1 week prior to study treatment and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated.
The Estimated Number of Participants
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Taiwan
160 participants
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Global
0 participants
