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

A Phase 1b/2 Trial of Hu5F9-G4 in Combination With Rituximab or Rituximab + Chemotherapy in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: Magrolimab; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd
• United Kingdom
  • Oxford, United Kingdom, OX3 7LE
    • The Churchill Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35924
      • University of Alabama at Birmingham (UAB)
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical center
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center/ National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center, Fairview
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Siteman Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: MabThera; RITUXAN®
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: MabThera; RITUXAN®
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: MabThera; RITUXAN®
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: MabThera; RITUXAN®; 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: MabThera; RITUXAN®; 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs)	DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment in participant in Phase 1b.	Up to 28 days
Percentage of Participants Experiencing Treatment Emergent Adverse Events		First dose date up to 5 years
Objective Response Rate as Defined by the Investigator According to the Lugano Classification for Lymphomas	Objective response is defined as complete response (CR) + partial response (PR) determined by Lugano classification for lymphomas.	Up to 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter of Magrolimab: AUClast	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
PK Parameter of Rituximab: AUClast	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
PK Parameter of Magrolimab: AUCtau	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
PK Parameter of Rituximab: AUCtau	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
PK Parameter of Magrolimab: Cmax	Cmax is defined as the maximum observed concentration of drug.	Before magrolimab infusion (within 12 hours) on Day 1, 8, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycles 3, 4, 5, 9, and 13 and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
PK Parameter of Rituximab: Cmax	Cmax is defined as the maximum observed concentration of drug.	Before rituximab infusion (within 12 hours) on Day 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycles 3 - 6; Cycle length is 28 days
Percentage of Participants who Developed Anti-Magrolimab Antibodies		Day 1 of Cycle 1 to 5, Day 1 Cycle 9, 13, and until safety follow-up visit (30 days ± 7 days after last dose of magrolimab); Cycle length is 28 days
Duration of Response	The duration of response is measured from when the first (objective) response is met (i.e., complete response or partial response) until the first date of objectively documented progressive disease.	Up to 5 years
Progression Free Survival	Progression free survival is measured from dose initiation until the first date of objectively documented disease progression or death.	Up to 5 years
Overall Survival	Overall Survival is measured from dose initiation until death.	Up to 5 years
Time to Progression	Time to Progression is measured from dose initiation until the first date of objectively documented progressive disease criteria.	First dose date up to 5 years
Objective Rate of Response Defined by the Investigator According to the LYRIC Criteria for Lymphomas	Objective response is defined as complete response + partial response determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.	Up to 5 months

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: The Leukemia and Lymphoma Society
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Advani R, Flinn I, Popplewell L, Forero A, Bartlett NL, Ghosh N, Kline J, Roschewski M, LaCasce A, Collins GP, Tran T, Lynn J, Chen JY, Volkmer JP, Agoram B, Huang J, Majeti R, Weissman IL, Takimoto CH, Chao MP, Smith SM. CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma. N Engl J Med. 2018 Nov 1;379(18):1711-1721. doi: 10.1056/NEJMoa1807315.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: November 1, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimated): November 2, 2016

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Oxaliplatin; Rituximab; Magrolimab; Gemcitabine
• Other Study ID Numbers: 5F9003; 2016-003408-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No