Clinical Trials List
Protocol NumberD967LC00001
NCT Number(ClinicalTrials.gov Identfier)NCT04379596
Active
2020-06-26 - 2026-12-31
Phase I/II
Recruiting6
ICD-10C16.9
Malignant neoplasm of stomach, unspecified
ICD-10C7A.092
Malignant carcinoid tumor of the stomach
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9151.9
Malignant neoplasm of stomach, unspecified
A Phase 1b/2 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants with HER2-Overexpressing Gastric Cancer (DESTINY-Gastric03)
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Trial Applicant
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Sponsor
AstraZneca AB
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Chung-Pin Li Digestive System Department
- Yun-Cheng Hsieh Digestive System Department
- Chien-An Liu Division of Others -
- Shao-Jung Hsu Digestive System Department
- Yee Chao Division of Hematology & Oncology
- San-Chi Chen Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Radiation Therapy
- Yi-Ping Hung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chiun Hsu Division of Hematology & Oncology
- 陳國興 Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- Hsin-Yu Liu Division of Ophthalmology
- Chih-Hung Hsu Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- Hsiang-Fong Kao Division of General Internal Medicine
- 梁逸歆 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tsai-Sheng Yang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- 吳教恩 Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Wen-Chi Shen Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蘇勇曄 Division of Hematology & Oncology
- 劉奕廷 Division of Hematology & Oncology
- Hui-Jen Tsai Division of Hematology & Oncology
- Chia-Jui Yen Division of General Internal Medicine
- Chien-Jui Huang Division of Hematology & Oncology
- Nai-Jung Chiang 未分科
- 趙盈瑞 Division of Hematology & Oncology
- 顏志傑 Division of Hematology & Oncology
- Yan-Shen Shan Division of General Surgery
- 姜乃榕 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 吳佳哲 Division of Hematology & Oncology
- 黃詩喻 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 賴香蘭 Division of Hematology & Oncology
- 陳彥仰 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 郭明濬 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
HER2 overexpressing locally advanced or metastatic, unresectable Gastric Cancer.
Objectives
Primary objectives
1. Part 1: To assess safety and tolerability, and to determine the recommended Phase 2 dose (RP2D) or the highest protocol-defined dose of T-DXd combinations with capecitabine, infusional 5-fluorouracil, oxaliplatin or durvalumab
2. Part 2: To assess the antitumor activity of T-DXd combinations at the RP2D from Part 1
Secondary objectives
1. To assess the preliminary antitumor activity of T-DXd combinations
2. Part 2: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combination regimens
3. To assess the pharmacokinetics of T-DXd, total anti-HER2 antibody, MAAA-1181, and durvalumab in all arms
4. To investigate the immunogenicity of T-DXd
5. To assess antitumor activity based on comparison of local HER2 results with central retrospective HER2 testing from baseline tumor samples
Test Drug
Trastuzumab Deruxtecan
Active Ingredient
Trastuzumab Deruxtecan
Durvalumab
Durvalumab
Dosage Form
IVT
IVT
IVT
Dosage
100 mg
50 mg/ml
50 mg/ml
Endpoints
Part 1: To assess safety and tolerability, and to determine the recommended Phase 2 dose (RP2D) or the highest protocol-defined dose of T-DXd combinations with capecitabine, infusional 5-fluorouracil, oxaliplatin or durvalumab
Part 2: To assess the antitumor activity of T-DXd combinations at the RP2D from Part 1
Part 2: To assess the antitumor activity of T-DXd combinations at the RP2D from Part 1
Inclution Criteria
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative (Taiwan does not join this part).
3. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, or analyses.
4. Male and female participants must be at least 18 years of age at the time of signing the ICF. Participants in Japan must be at least 20 years of age at the time of signing the ICF. Other age restrictions may apply as per local regulations. (Taiwan >= 20 years of age)
5. Body weight > 30 kg.
6. Disease Characteristics:
(a) Locally advanced, unresectable, or metastatic disease based on most recent imaging
(b) Pathologically documented adenocarcinoma of the stomach or GEJ with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results.
7. For Part 1, progression on or after at least one prior trastuzumab-containing regimen (can include an approved trastuzumab biosimilar). Trastuzumab is not required to be a component of the most recent prior regimen.
8. For Part 2, previously untreated for unresectable or metastatic adenocarcinoma of the stomach or GEJ with HER2 overexpression. Prior neo-adjuvant and/or adjuvant therapy is acceptable, but all systemic therapy must have been completed at least 6 months prior to the diagnosis of unresectable or metastatic disease.
9. All participants must provide a formalin-fixed paraffin-embedded (FFPE) tumor sample for tissue-based IHC staining to determine HER2 expression and other correlatives. Tumor tissue can be either from the primary tumor or metastatic biopsy. If tumor tissue is unavailable, samples should not be collected specifically for this study but should be obtained as part of participant’s routine clinical care. Specimens with limited tumor content and fine needle aspirates are inadequate for defining tumor HER2 status. For additional details on sample requirements, see Section 8.6 of protocol.
(a) For Part 1, a recently collected tumor sample or an original diagnostic biopsy is required.
(b) For Part 2, a recently collected tumor sample taken after the participant’s last known treatment (if applicable) is required.
10. Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
11. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
12. Has LVEF ≥ 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before treatment allocation (Part 1) or randomization (Part 2).
13. Has adequate organ function within 14 days before treatment allocation (Part 1) or randomization (Part 2), defined in Protocol.
14. Has adequate treatment washout period before IP administration, defined in Protocol.
Reproduction
15. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner
(a) For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IP.
(b) Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
(i) Women aged ≥ 50 years would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the site.
(ii) Women aged ≤ 50 years would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
16. Female participants of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception (Table 12) from the time of screening, and must agree to continue using such precautions for at least 7 months after the last dose of IP. Not all methods of contraception are highly effective. Female participants must refrain from breastfeeding and must not donate (or retrieve for their own use) ova, from the time of screening, throughout the study treatment period, and for at least 7 months after the last dose of IP. Not engaging in sexual activity for the duration of the study and drug washout period is an acceptable practice; however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
17. Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to at least 4 months after the final dose of IP. Not engaging in sexual activity for the duration of the study and drug washout period is an acceptable practice; however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. It is strongly recommended for the female partners of a male participant to also use at least one highly effective method of contraception throughout this period, as described in. In addition, male participants should refrain from fathering a child or freezing or donating sperm from screening, throughout the study treatment period, and for at least 4 months after the last dose of IP.
2. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative (Taiwan does not join this part).
3. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, or analyses.
4. Male and female participants must be at least 18 years of age at the time of signing the ICF. Participants in Japan must be at least 20 years of age at the time of signing the ICF. Other age restrictions may apply as per local regulations. (Taiwan >= 20 years of age)
5. Body weight > 30 kg.
6. Disease Characteristics:
(a) Locally advanced, unresectable, or metastatic disease based on most recent imaging
(b) Pathologically documented adenocarcinoma of the stomach or GEJ with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results.
7. For Part 1, progression on or after at least one prior trastuzumab-containing regimen (can include an approved trastuzumab biosimilar). Trastuzumab is not required to be a component of the most recent prior regimen.
8. For Part 2, previously untreated for unresectable or metastatic adenocarcinoma of the stomach or GEJ with HER2 overexpression. Prior neo-adjuvant and/or adjuvant therapy is acceptable, but all systemic therapy must have been completed at least 6 months prior to the diagnosis of unresectable or metastatic disease.
9. All participants must provide a formalin-fixed paraffin-embedded (FFPE) tumor sample for tissue-based IHC staining to determine HER2 expression and other correlatives. Tumor tissue can be either from the primary tumor or metastatic biopsy. If tumor tissue is unavailable, samples should not be collected specifically for this study but should be obtained as part of participant’s routine clinical care. Specimens with limited tumor content and fine needle aspirates are inadequate for defining tumor HER2 status. For additional details on sample requirements, see Section 8.6 of protocol.
(a) For Part 1, a recently collected tumor sample or an original diagnostic biopsy is required.
(b) For Part 2, a recently collected tumor sample taken after the participant’s last known treatment (if applicable) is required.
10. Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
11. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
12. Has LVEF ≥ 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before treatment allocation (Part 1) or randomization (Part 2).
13. Has adequate organ function within 14 days before treatment allocation (Part 1) or randomization (Part 2), defined in Protocol.
14. Has adequate treatment washout period before IP administration, defined in Protocol.
Reproduction
15. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner
(a) For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IP.
(b) Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
(i) Women aged ≥ 50 years would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the site.
(ii) Women aged ≤ 50 years would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
16. Female participants of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception (Table 12) from the time of screening, and must agree to continue using such precautions for at least 7 months after the last dose of IP. Not all methods of contraception are highly effective. Female participants must refrain from breastfeeding and must not donate (or retrieve for their own use) ova, from the time of screening, throughout the study treatment period, and for at least 7 months after the last dose of IP. Not engaging in sexual activity for the duration of the study and drug washout period is an acceptable practice; however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
17. Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to at least 4 months after the final dose of IP. Not engaging in sexual activity for the duration of the study and drug washout period is an acceptable practice; however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. It is strongly recommended for the female partners of a male participant to also use at least one highly effective method of contraception throughout this period, as described in. In addition, male participants should refrain from fathering a child or freezing or donating sperm from screening, throughout the study treatment period, and for at least 4 months after the last dose of IP.
Exclusion Criteria
1. Lack of physiological integrity of the upper gastrointestinal tract, or malabsorption syndrome.
2. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
3. Grade >=2 peripheral neuropathy or hearing loss.
4. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent
5. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrolment.
6. Participants with a medical history of myocardial infarction within 6 months before treatment allocation (Part 1) or randomization (Part 2), symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out myocardial infarction.
7. Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on average of the screening triplicate 12-lead ECG.
8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
(a) Participants with vitiligo or alopecia
(b) Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
(c) Any chronic skin condition that does not require systemic therapy
(d) Participants without active disease in the last 5 years may be included but only after consultation with the Study Physician
(e) Participants with celiac disease controlled by diet alone.
9. History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
10. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within three months of treatment allocation/randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis etc), and prior pneumonectomy.
11. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
12. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- Participants should be tested for HIV prior to treatment allocation (Part 1) or randomization (Part 2) if required by local regulations or by the IRB/IEC.
- Participants positive for hepatitis C antibody are eligible only if a polymerase chain reaction is negative for HCV RNA.
13. Multiple primary malignancies within the prior 3 years, except adequately resected non melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated.
14. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). Drainage and CART are not allowed within 2 weeks prior to screening assessment.
Prior/Concomitant Therapy
15. Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
16. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Participants with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Study Physician or designee (eg, Grade 2 chemotherapy-induced neuropathy).
17. Known allergy or hypersensitivity to any IPs or any of the study drug excipients.
18. Pregnant or breastfeeding female participants.
19. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at the study site).
20. Judgment by the Investigator that the participant should not participate in the study, if the participant is unlikely to comply with study procedures, restrictions, and requirements.
21. Previous treatment allocation or randomization in the present study.
2. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
3. Grade >=2 peripheral neuropathy or hearing loss.
4. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent
5. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrolment.
6. Participants with a medical history of myocardial infarction within 6 months before treatment allocation (Part 1) or randomization (Part 2), symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out myocardial infarction.
7. Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on average of the screening triplicate 12-lead ECG.
8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
(a) Participants with vitiligo or alopecia
(b) Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
(c) Any chronic skin condition that does not require systemic therapy
(d) Participants without active disease in the last 5 years may be included but only after consultation with the Study Physician
(e) Participants with celiac disease controlled by diet alone.
9. History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
10. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within three months of treatment allocation/randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis etc), and prior pneumonectomy.
11. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
12. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- Participants should be tested for HIV prior to treatment allocation (Part 1) or randomization (Part 2) if required by local regulations or by the IRB/IEC.
- Participants positive for hepatitis C antibody are eligible only if a polymerase chain reaction is negative for HCV RNA.
13. Multiple primary malignancies within the prior 3 years, except adequately resected non melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated.
14. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). Drainage and CART are not allowed within 2 weeks prior to screening assessment.
Prior/Concomitant Therapy
15. Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
16. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Participants with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Study Physician or designee (eg, Grade 2 chemotherapy-induced neuropathy).
17. Known allergy or hypersensitivity to any IPs or any of the study drug excipients.
18. Pregnant or breastfeeding female participants.
19. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at the study site).
20. Judgment by the Investigator that the participant should not participate in the study, if the participant is unlikely to comply with study procedures, restrictions, and requirements.
21. Previous treatment allocation or randomization in the present study.
The Estimated Number of Participants
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Taiwan
25 participants
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Global
463 participants
