Study of Magrolimab (Hu5F9-G4) in Combination With Avelumab in Solid Tumor Participants and Checkpoint-Inhibitor-Naive Ovarian Cancer Participants Who Progress Within 6 Months of Prior Platinum Chemotherapy

Ovarian Cancer Clinical Trial

Official title:

A Phase 1b Trial of Hu5F9-G4 in Combination With Avelumab in Solid Tumor Patients and Checkpoint-Inhibitor-Naive Ovarian Cancer Patients Who Progress Within 6 Months of Prior Platinum Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03558139
• Other study ID #: 5F9006
• Status: Completed
• Phase: Phase 1
• Start date: May 23, 2018
• Est. completion date: December 3, 2020

Study information

• Verified date: September 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to investigate the safety and tolerability of magrolimab in combination with avelumab in participants with advanced solid tumors and to confirm the safety and tolerability of this combination and evaluate the anti-tumor activity in participants with checkpoint inhibitor-naive ovarian cancer, fallopian tube cancer, and primary peritoneal carcinoma who have previously progressed within 1-6 months of receiving platinum chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 3, 2020
• Est. primary completion date: December 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Safety Run-in Cohort: Pathologically confirmed advanced solid tumors.

• Ovarian Cancer Expansion Cohort: Histologically or cytologically confirmed, epithelial ovarian, fallopian tube, or peritoneal cancer.

• Checkpoint inhibitor naive participants.

• Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy.

• Adequate performance status. Adequate hematological, liver, and kidney functions.

• Availability of pre-treatment tumor tissue to evaluate programmed cell death-ligand 1(PD-L1) expression.

Key Exclusion Criteria:

• Individuals with symptomatic or untreated central nervous system (CNS) metastases.

• Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPa) targeting agents.

• Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV).

• Red blood cell transfusion dependence.

• Prior organ transplantation requiring immunosuppression or active autoimmune disease.

• Significant medical diseases and/or history of uncontrolled intercurrent illness or other serious medical condition.

• Pregnancy or active breast feeding.

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Magrolimab
Administered intravenously
• Avelumab
Administered intravenously

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lakhani NJ, Patnaik A, Liao JB, et al. A phase 1b study of the anti-CD47 antibody magrolimab with the PD-L1 inhibitor avelumab in solid tumor & ovarian cancer patients [Abstract]. American Society of Clinical Oncology (ASCO)-Society for Immunotherapy of C

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1)	A DLT was defined as a = Grade 3 AE that was assessed as related to either magrolimab or avelumab that occurred during the 5-week DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.	From the first dose date up to 5 weeks
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Treatment-emergent AEs were defined as those AEs that worsened or occurred during or after a participant's first dose of any study treatment and those existing AEs that worsened during the study and within 30 days after the last administration of any study treatment or initiation of subsequent anticancer therapy, whichever occurred first.	First dose date up to last dose plus 30 days (maximum treatment duration 18.3 months)
Primary	Percentage of Participants With Objective Response (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 in Participants With Ovarian Cancer	Objective response was defined as the percentage of participants with objective response which consisted of complete response (CR)+ partial response (PR) determined by RECIST v 1.1. CR: Disappearance of all target and all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)
Secondary	Recommended Phase 2 Dose and Schedule (RP2DS) of Magrolimab in Combination With Avelumab	The RP2DS was the dose of magrolimab in combination with avelumab with DLT rate less than 33% in at least 6 evaluable participants in Part 1. A DLT was defined as a = Grade 3 AE that was assessed as related to either magrolimab or avelumab that occurred during the 5-week DLT assessment period with protocol-defined allowed exceptions. Any TEAE that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.	From the first dose date up to 5 weeks
Secondary	Serum Concentrations of Magrolimab - Safety Run-in (Part 1)	Serum concentrations will be drawn at pre-study drug infusion (within 12 hours) on Day (D) 1 and 22 in Cycle (C) 1; Days 1 and 15 in Cycle 2; Day 1 in Cycles 3 and 4; every 3rd cycle on Day 1 until Cycle 13; 1 hour post-magrolimab infusion on Days 1 and 8 in Cycle 1; 24 hours post magrolimab infusion (Part 1 only) on Days 1 and 8 in Cycle 1; pre-study drug infusion on Day 1 in Cycles 5 and 11 (Part 1 Magrolimab 45 mg/kg only); End of Treatment (EOT) visit (up to Cycle 13); Safety Follow-up Visit (30 days after last dose of magrolimab, maximum treatment duration 18.3 months). Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days.	Predose: (C1D1, C1D22, C2D1,C2D15, C3D1, C4D1, C5D1 [only for 45 mg/kg Part 1], C7D1, C10D1, C11D1 [only for 45 mg/kg Part 1], C13D1, EOT, Safety Follow-up); 1 hour postdose: (C1D1, C1D8); 24 hours postdose: (C1D1, C1D8)
Secondary	Percentage of Participants With Transient Anti-Drug Antibody to Magrolimab - Safety Run-in (Part 1)		From Day 1 of Cycle 1 up to Safety Follow-up (30 days after last dose of magrolimab, maximum treatment duration 18.3 months); Cycle 1: 35 days, subsequent Cycles: 28 days.
Secondary	Percentage of Participants With Objective Response According to Gynecologic Cancer InterGroup (GCIG) Criteria in Ovarian Cancer	Objective response was defined as participants with a CR or a PR as assessed per GCIG criteria. The GCIG proposed use of both the RECIST and cancer antigen 125 (CA-125) criteria. A response according to CA-125 has occurred if there is = 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Participants can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the upper limit of normal (ULN) and within 2 weeks prior to starting treatment. According to RECIST 1.1, CR was defined as disappearance of all target and all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters.	From Screening until 26.2 months (assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days)
Secondary	Duration of Response (DOR) as Per GCIG Criteria in Participants With Ovarian Cancer	DOR: time from initial response (CR or PR) until disease progression. Disease progression was defined according to RECIST 1.1 but can also be based on serum CA-125. Progression based on serum CA-125 levels was defined as (1) elevated CA-125 pretreatment and normalization of CA-125 with evidence of CA-125 =2x ULN on 2 occasions at least 1 week apart or; (2) elevated CA-125 pretreatment, which never normalizes, with evidence of CA-125 =2x nadir value on 2 occasions at least 1 week apart or; (3) CA-125 in normal range pretreatment with evidence of CA-125 =2x ULN on 2 occasions at least 1 week apart.; Progression per RECIST 1.1: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum measured while on study (this included baseline sum if that was smallest). In addition to relative increase of 20%, sum must also demonstrate absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesion.	From initial response until disease progression or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
Secondary	Progression-free Survival (PFS) in Participants With Ovarian Cancer	PFS was defined as the duration of time from dose initiation to the first date of objectively documented disease progression per RECIST 1.1 or death, whichever occurred at first. Progression as per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Participants who did not have documented disease progression and did not die were censored at their last tumor assessment date. Kaplan-Meier estimate was used for analysis	From first dose date to disease progression, death or maximum time on study (26.2 months); assessed on Day 1 of Cycle 3 then every 2 cycles from Cycle 5 onwards up to 26.2 months; 1 cycle: 28 days
Secondary	Overall Survival (OS) in Participants With Ovarian Cancer	OS was defined as the duration of time from dose initiation to the date of death due to any cause. Participants who did not die were censored at their last known alive date.; Kaplan-Meier estimate was used for analysis.	From first dose date to death or maximum time on study (26.2 months)
Secondary	Percent Change of Immune Cells by Immunohistochemistry in Participants With Ovarian Cancer	Paired tumor biopsies from participants with ovarian cancer were analyzed by CD68 immunohistochemistry staining to evaluate the impact of magrolimab in combination with avelumab on macrophage frequency in the tumor microenvironment.	Screening and Day 1 Cycle 3 (Cycle 3 duration: 28 days)

External Links

•   Gilead Clinical Trials Website