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

Purpose

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.

Condition

  • Non Hodgkin Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 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

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Magrolimab + Rituximab, Phase 1b Dose Escalation
Participants with B-cell non-Hodgkin's lymphoma will receive 1 mg/kg magrolimab priming dose on Day 1 of Cycle 1 followed by weekly maintenance doses of 10, 20, 30, or 45 mg/kg on Days 8, 15, 22 for Cycle 1 and Days 1, 8, 15, and 22 for each cycle to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose and schedule (RP2DS) in combination with rituxumab 375 mg/m^2. Cycle length is 28 days.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
  • Drug: Rituximab
    Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
    Other names:
    • RITUXAN®
    • MabThera
Experimental
Magrolimab + Rituximab, Phase 2 Indolent Lymphoma
Participants with indolent lymphoma will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
  • Drug: Rituximab
    Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
    Other names:
    • RITUXAN®
    • MabThera
Experimental
Magrolimab + Rituximab, Phase 2 Diffuse Large B-Cell lymphoma
Participants with diffuse large B-cell lymphoma (DLBCL) will receive magrolimab based on RP2DS from Phase 1b portion of the study in combination with rituxumab 375 mg/m^2.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
  • Drug: Rituximab
    Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
    Other names:
    • RITUXAN®
    • MabThera
Experimental
Magrolimab + R-GemOx, Phase 1b Safety Dose Escalation Phase
Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive 1 mg/kg magrolimab priming dose on Day 1 for Cyle 1 followed by maintenance doses of 30 or 45 mg/kg on Days 8, 11, 15, 22, and 29 for Cycle 1, every week for Cycle 2, and every 2 weeks for each cycle to determine maximum tolerated dose (MTD) + rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2. Cycle length is 28 days.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
  • Drug: Rituximab
    Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
    Other names:
    • RITUXAN®
    • MabThera
  • Drug: Gemcitabine
    Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
    Other names:
    • Gemzar®
  • Drug: Oxaliplatin
    Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
    Other names:
    • Eloxatin®
Experimental
Magrolimab + R-GemOx, Phase 1b Dose Expansion Phase
Autologous stem cell transplant (or transplantation) ineligible DLBCL participants will receive magrolimab at a dose determined from Phase 1b Safety Dose-Escalation Phase in combination with rituxumab 375 mg/m^2 + gemcitabine 1000 mg/m^2 + oxaliplatin 100 mg/m^2.
  • Drug: Magrolimab
    Administered intravenously
    Other names:
    • Hu5F9-G4
  • Drug: Rituximab
    Administered intravenously on Days 8, 15, and 22 during Cycle 1, followed by 1 dose on Day 1 for Cycles 2 through 6, and Day 1 for every other cycle until Cycle 13
    Other names:
    • RITUXAN®
    • MabThera
  • Drug: Gemcitabine
    Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
    Other names:
    • Gemzar®
  • Drug: Oxaliplatin
    Administered intravenously on Days 11, 23 for Cycle 1 and Days 2 and 15 for Cycles 2 to 4
    Other names:
    • Eloxatin®

More Details

Status
Active, not recruiting
Sponsor
Gilead Sciences

Study Contact