Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Gilead Sciences

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Non Hodgkin Lymphoma

Treatments: Drug: Rituximab; Drug: Oxaliplatin; Drug: Gemcitabine; Drug: Magrolimab; Drug: Allopurinol

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02953509

5F9003

2016-003408-29 (EudraCT Number)

Details and patient eligibility

About

The primary objectives of this study are:

• To investigate the safety and tolerability, and to define the recommended Phase 2 dose and schedule (RP2DS) for magrolimab in combination with rituximab and for magrolimab in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx).
• To evaluate the efficacy of magrolimab in combination with rituximab in participants with indolent lymphoma and diffuse large B-cell lymphoma (DLBCL) and to evaluate the efficacy of magrolimab in combination with R-GemOx in autologous stem cell transplant (ASCT) ineligible DLBCL participants.

Enrollment: 178 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Phase 1b only: B-cell non-Hodgkin's lymphoma (NHL), relapsed or refractory to standard approved therapies
• DLBCL Phase 2 cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL) expressing cluster of differentiation (CD) 20, relapsed or refractory to at least 2 prior lines treatment containing anti-CD20 therapy
• Indolent lymphoma Phase 2 cohort: Marginal zone or follicular lymphoma, relapsed or refractory to standard approved therapies
• DLBCL chemotherapy combination cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL), relapsed or refractory to 1-3 prior lines of treatment
• Adequate performance status and hematological, liver and kidney functions
• Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy

Key Exclusion Criteria:

• Active brain metastases
• Prior allogeneic hematopoietic cell transplantation
• Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents
• Second malignancy within the last 3 years
• Known active or chronic hepatitis B or C infection or HIV
• Pregnancy or active breastfeeding
• Prior chimeric antigen receptor (CAR-T) therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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178 participants in 10 patient groups

Phase 1b Cohort 1: Magrolimab 10 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell non-hodgkin's lymphoma (NHL) will receive 1 mg/kg magrolimab intravenous (IV) infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 10 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 1b Cohort 2: Magrolimab 20 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 20 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 1b Cohort 3: Magrolimab 30 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11,15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 1b Cohort 4: Magrolimab 45 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell NHL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 45 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1 and Days 1, 8, 15, and 22 of Cycle 2 and beyond in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 1b Cohort 5: Magrolimab 30 mg/kg + Rituximab + Gemcitabine + Oxaliplatin

Experimental group

Description:

Autologous stem cell transplant ineligible diffuse large B-cell lymphoma (DLBCL) participants will receive 1 mg/kg magrolimab IV infusion priming dose(over 3 hours)on Day 1 of Cycle 1,followed by maintenance dose of 30 mg/kg on Days 8, 11, 15, 22, and 29 of Cycle 1;Days 1, 8, 15, and 22 of Cycle 2 followed by Days 1 and 15 of subsequent cycles.Cycle length will be 28 days.Rituximab 375 mg/m\^2 IV infusion will be given on Days 8, 15, 22, and 29 of Cycle 1,followed by 1 dose on Day 1 of Cycles 2 to 6.Thereafter from Cycle 8 and beyond,rituximab will be administered on Day 1 of every other cycle(on even cycles).Gemcitabine 1000 mg/m\^2 and oxaliplatin 100 mg/m\^2 IV infusion will be given as on Days 11 and 23 of Cycle 1 and Days 2 and 15 of Cycles 2 to 4.Granulocyte colony stimulating factor (G-CSF) prophylaxis will be given with gemcitabine and oxaliplatin treatment(Cycles 1-4).Allopurinol 300 mg orally daily will be administered for the first cycle only.

Treatment:

Drug: Allopurinol

Drug: Magrolimab

Drug: Oxaliplatin

Drug: Gemcitabine

Drug: Rituximab

Phase 1b Cohort 6: Magrolimab 45 mg/kg + Rituximab + Gemcitabine + Oxaliplatin

Experimental group

Description:

Autologous stem cell transplant ineligible DLBCL participants will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by maintenance dose of 45 mg/kg on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 followed by Days 1 and 15 of subsequent cycles. The cycle length of 28 days. Rituximab 375 mg/m\^2 IV infusion will be administered on Days 8, 15, 22, and 29 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Gemcitabine 1000 mg/m\^2 and oxaliplatin 100 mg/m\^2 IV infusion will be administered as on Days 11 and 23 of Cycle 1 and Days 2 and 15 of Cycles 2 to 4. G-CSF prophylaxis will be administered with gemcitabine and oxaliplatin treatment (Cycles 1-4). Allopurinol 300 mg orally daily will be administered for the first cycle only.

Treatment:

Drug: Allopurinol

Drug: Magrolimab

Drug: Oxaliplatin

Drug: Gemcitabine

Drug: Rituximab

Phase 2 Cohort 1: Magrolimab 30 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell indolent NHL (iNHL) (including follicular lymphoma \[FL\] and marginal zone lymphoma \[MZL\]) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1, and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 of Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 2 Cohort 2: Magrolimab 30 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell iNHL (including FL and MZL) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 2 Cohort 3: Magrolimab 45 mg/kg + Rituximab

Experimental group

Description:

Participants with B-cell iNHL (including FL and MZL) and DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 45 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab

Phase 2 Cohort 4: Magrolimab 30 mg/kg + Rituximab

Experimental group

Description:

Participants with DLBCL will receive 1 mg/kg magrolimab IV infusion priming dose (over 3 hours) on Day 1 of Cycle 1, followed by weekly maintenance dose of 30 mg/kg magrolimab IV infusion (over 2 hours) on Days 8, 15, and 22 of Cycle 1; Days 1, 8, 15, and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles in combination with rituximab 375 mg/m\^2 IV infusion on Days 8, 15, and 22 of Cycle 1, followed by 1 dose on Day 1 for Cycles 2 to 6. Thereafter from Cycle 8 and beyond, rituximab will be administered on Day 1 of every other cycle (on even cycles). Each Cycle length of 28 days.

Treatment:

Drug: Magrolimab

Drug: Rituximab