A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma

MedImmune

Status and phase: Completed; Phase 2; Phase 1

Conditions: Gastric or Gastroesophageal Junction Adenocarcinoma

Treatments: Biological: MEDI4736+tremelimumab; Biological: Tremelimumab; Biological: MEDI4736; Biological: MEDI4736 + tremelimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02340975

D4190C00021

Details and patient eligibility

About

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.

Enrollment: 114 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 6 patient groups

Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)

Experimental group

Description:

Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma will receive intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Treatment:

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab

Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Experimental group

Description:

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Treatment:

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab

Phase 2 Arm B-M10 mg/kg (Q2W)

Experimental group

Description:

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).

Treatment:

Biological: MEDI4736

Phase 2 Arm C-T10 mg/kg (Q4W)

Experimental group

Description:

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).

Treatment:

Biological: Tremelimumab

Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Experimental group

Description:

Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Treatment:

Biological: MEDI4736+tremelimumab

Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Experimental group

Description:

Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Treatment:

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab

Biological: MEDI4736 + tremelimumab