Clinical trial NCT02340975: A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma
Official title: A Phase 1b/2 Study of MEDI4736 in Combination With Tremelimumab, MEDI4736 Monotherapy, and Tremelimumab Monotherapy in Subjects With Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gastric or Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Immunotherapy
Antibodies, Monoclonal
Tremelimumab
MEDI4736
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab, MEDI4736 monotherapy or tremelimumab monotherapy in participants with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma.


Eligibility criteria: Inclusion Criteria:

1. Male and female participants
2. 18 years and older
3. Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma
4. Participants must have received and have progressed, or are refractory to standard regimens
5. Participants must have at least one lesion amenable to biospy

Exclusion Criteria:

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
2. Previous immunotherapy
3. Concurrent or prior use of immunosuppressive medication with 14 days
4. Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b
timeFrame: From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
timeFrame: Baseline (Day 1)
measure: Percentage of Participants With Objective Response (OR) in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Progression Free Survival at 6 (PFS-6) Month in Phase 2
timeFrame: From Day 1 upto 6 months
Secondary outcomes:
measure: Percentage of Participants With Objective Response in Phase 1b
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Duration of Stable Disease (DSD) in Phase 1b
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Percentage of Participants With Disease Control at 16 Weeks in Phase 1b
timeFrame: From Day 1 up to 16 weeks
measure: Percentage of Participants With Disease Control at 24 Weeks in Phase 1b
timeFrame: From Day 1 up to 24 weeks
measure: Progression Free Survival at 6 Month in Phase 1b
timeFrame: From Day 1 upto 6 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
timeFrame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
timeFrame: Baseline (Day 1)
measure: Percentage of Participants With Disease Control at 16 Weeks in Phase 2
timeFrame: From Day 1 up to 16 weeks
measure: Percentage of Participants With Disease Control at 24 Weeks in Phase 2
timeFrame: From Day 1 up to 24 weeks
measure: Duration of Response (DoR) in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Time to Response (TTR) in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Duration of Stable Disease in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Progression Free Survival in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Progression Free Survival at 9 Month (PFS-9) in Phase 2
timeFrame: From Day 1 up to 9 months
measure: Overall Survival (OS) in Phase 2
timeFrame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
measure: Overall Survival at 12 Months in Phase 2
timeFrame: From Day 1 up to 12 months
measure: Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2
timeFrame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
measure: Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2
timeFrame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
measure: Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
timeFrame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune, LLC MedImmune, LLC
role: STUDY_DIRECTOR
References: