Neoplasm, Gastrointestinal Clinical Trial
Official title:
A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
| Verified date | March 2022 |
| Source | Daiichi Sankyo, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.
| Status | Completed |
| Enrollment | 233 |
| Est. completion date | December 11, 2020 |
| Est. primary completion date | November 8, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 20 Years and older |
| Eligibility | Inclusion Criteria: 1. Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction 2. Progression on and after at least 2 prior regimens 3. Has an adequate tumor sample 4. Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 Exclusion Criteria: 1. Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia 2. Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females 3. Has a medical history of clinically significant lung disease 4. Is suspected to have certain other protocol-defined diseases based on imaging at screening period 5. Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise: 1. safety or well-being of the participant or offspring 2. safety of study staff 3. analysis of results |
| Country | Name | City | State |
|---|---|---|---|
| Japan | Hyogo Cancer Center | Akashi | Hyogo |
| Japan | Kansai Rosai Hospital | Amagasaki | Hyogo |
| Japan | Tokyo Metropolitan Komagome Hospital | Bunkyo-Ku | Tokyo |
| Japan | Chiba Cancer Center | Chiba | |
| Japan | National Cancer Center Hospital | Chuo Ku | Tokyo |
| Japan | Fukui Prefectural Hospital | Fukui | |
| Japan | Kyushu University Hospital | Fukuoka | |
| Japan | National Hospital Organization Kyushu Cancer Center | Fukuoka | |
| Japan | Gifu University Hospital | Gifu | |
| Japan | Hirosaki University Hospital | Hirosaki | Aomori |
| Japan | Hiroshima City Asa Citizens Hospital | Hiroshima | |
| Japan | Hiroshima Prefectural Hospital | Hiroshima | |
| Japan | Japanese Red Cross Kyoto Daini Hospital | Kamigyo-ku | Kyoto |
| Japan | Kanazawa University Hospital | Kanazawa | Ishikawa |
| Japan | Ibaraki Prefectural Central Hospital | Kasama | Ibaraki |
| Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
| Japan | St. Marianna University School of Medicine Hospital | Kawasaki | Kanagawa |
| Japan | Kagawa University Hospital | Kita | Kagawa |
| Japan | Japan Community Health Care Organization Kyushu Hospital | Kitakyushu | Fukuoka |
| Japan | Kobe City Medical Center General Hospital | Kobe | Hyogo |
| Japan | Kochi Health Sciences Center | Kochi | |
| Japan | Showa University Koto Toyosu Hospital | Koto-Ku | Tokyo |
| Japan | The Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-Ku | Tokyo |
| Japan | Kure Medical Center | Kure | Hiroshima |
| Japan | National Hospital Organization Shikoku Cancer Center | Matsuyama | Ehime |
| Japan | Toranomon Hospital | Minato-Ku | Tokyo |
| Japan | Aichi Cancer Center Hospital | Nagoya | Aichi |
| Japan | Miyagi Cancer Center | Natori | Miyagi |
| Japan | Niigata Cancer Center Hospital | Niigata | |
| Japan | Okayama University Hospital | Okayama | |
| Japan | Kindai University Hospital | Osaka | |
| Japan | Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital | Osaka | |
| Japan | Osaka General Medical Center | Osaka | |
| Japan | Osaka International Cancer Institute | Osaka | |
| Japan | Osaki Citizen Hospital | Osaki | Miyagi |
| Japan | Gunma Prefectural Cancer Center | Ota | Gunma |
| Japan | The Kitasato Institute Kitasato University Hospital | Sagamihara | Kanagawa |
| Japan | Saitama Cancer Center | Saitama | |
| Japan | Hokkaido University Hospital | Sapporo | Hokkaido |
| Japan | Iwate Medical University Hospital | Shiwa-gun | Iwate |
| Japan | Shizuoka Cancer Center | Shizuoka | |
| Japan | Shizuoka General Hospital | Shizuoka | |
| Japan | Osaka University Hospital | Suita | Osaka |
| Japan | Keio University Hospital | Tokyo | |
| Japan | Toyonaka Municipal Hospital | Toyonaka | Osaka |
| Japan | Tochigi Cancer Center | Utsunomiya | Tochigi |
| Japan | Kanagawa Cancer Center | Yokohama | Kanagawa |
| Japan | Yokohama City University Medical Center | Yokohama | Kanagawa |
| Korea, Republic of | Dong-A University Hospital | Busan | |
| Korea, Republic of | Inje University Haeundae Paik Hospital | Busan | |
| Korea, Republic of | Chungbuk National University Hospital | Cheongju-si | Chungcheongbuk-do |
| Korea, Republic of | Kyungpook National University Chilgok Hospital | Daegu | |
| Korea, Republic of | Chonnam National University Hwasun Hospital | Gwangju | |
| Korea, Republic of | National Cancer Center | Ilsan | Gyeonggi-do |
| Korea, Republic of | Gachon University Gil Medical Center | Incheon | |
| Korea, Republic of | Chonbuk National University Hospital | Jeonju | |
| Korea, Republic of | Seoul National University Bundang Hospital | Seongnam | |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Chung-Ang University Hospital | Seoul | |
| Korea, Republic of | Gangnam Severance Hospital | Seoul | |
| Korea, Republic of | Korea University Anam Hospital | Seoul | |
| Korea, Republic of | Korea University Guro Hospital | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | |
| Korea, Republic of | Yonsei Cancer Center, Severance Hospital, Yonsei University Health System | Seoul |
| Lead Sponsor | Collaborator |
|---|---|
| Daiichi Sankyo Co., Ltd. | AstraZeneca |
Japan, Korea, Republic of,
Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positiv — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported. | Baseline to date of first documented objective response (CR or PR), up to 36 months postdose | |
| Primary | Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on RECIST version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported. | Baseline to date of first documented objective response, up to 36 months postdose | |
| Secondary | Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause. | From the date of randomization to the date of death (due to any cause), up to 36 months postdose | |
| Secondary | Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions. | From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 36 months postdose | |
| Secondary | Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) | Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only. | From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 36 months postdose | |
| Secondary | Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. | Baseline to date of first documented objective response (CR, PR, and SD), up to 36 months postdose | |
| Secondary | Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) | The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on RECIST version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported. | From randomization to first documented objective response, up to 36 months postdose | |
| Secondary | Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) | Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation. | From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 36 months postdose | |
| Secondary | Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set) | The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on RECIST version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported. | From randomization to first documented objective response, up to 36 months postdose | |
| Secondary | Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a | Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods. | Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days) | |
| Secondary | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set) | A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs. | Baseline up to 47 days after last dose, up to 36 months postdose | |
| Secondary | Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) =20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set) | A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. | Baseline up to 47 days after last dose, up to 36 months postdose |