Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Avelumab

Magrolimab

Antineoplastic Agents, Immunological

Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 15, 22, and 29 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Participants with solid tumors will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Participants with checkpoint inhibitor-naïve ovarian cancer will be treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 will consist of 35 days and Cycle 2 and subsequent cycle will consist of 28 days. Avelumab will be administered 1 hour prior to magrolimab infusion on days when both are given. Treatment will be administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Gilead Study Director

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

Merck KGaA, Darmstadt, Germany

Gilead Sciences

Adverse Events: All treated participants included all participants who received at least 1 dose of any study drugs.

All-Cause Mortality: All participants enrolled in study were analyzed. Per planned analysis, AE data were summarized by magrolimab maintenance dose level. One participant in Part 2 received maintenance dose of 20 mg/kg. Because of confidentiality reason, data for this participant was not provided separately and included in "Magrolimab Priming Dose or Magrolimab 20 mg/kg" arm.

Participants with solid tumors were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 15, 22, and 29 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)

Participants with solid tumors (Part 1) or checkpoint inhibitor-naive ovarian cancer (Part 2) were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1 and Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in + Part 2, Ovarian Cancer Expansion)

Participants who received only priming dose of magrolimab (1 mg/kg) in Part 2 of the study.

For 1 participant (Part 2) magrolimab infusion was not completed at the first maintenance dose because of adverse event and \<60% of planned dose was administered. Subsequently the participant was treated at 20 mg/kg dose level.

Magrolimab Priming Dose or Magrolimab 20 mg/kg

Participants with solid tumors were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1 and Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)

Participants with checkpoint inhibitor-naïve ovarian cancer were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The data for mean baseline CD68 macrophage was not collected for participants in Part 1, Safety Run-in Cohorts. Data are reported for the participants who enrolled in Ovarian Cancer Expansion Cohort (Part 2) and for whom paired biopsies were available.

CD68 Macrophages

All Treated participants included all participants who received at least 1 dose of any study drugs.

Gilead Clinical Study Information Center

DLT evaluable participants: Participants in the Safety Run-in Part who met if either of the following criteria during the DLT assessment period:

* the participant experienced a DLT at any time after initiation of the first infusion of either magrolimab or avelumab and during the 5-week DLT assessment period
* the participant completed at least 4 (or 5 if assigned to magrolimab 45 mg/kg + avelumab 800 mg) infusions of magrolimab at the assigned dose and 2 infusions of avelumab.

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1)

Participants with solid tumors (Part 1) or checkpoint inhibitor-naive ovarian cancer (Part 2) were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1 and Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles. Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

All Treated participants (included all participants who received at least 1 dose of any study drugs) were analyzed. Per planned analysis, AE data were summarized by the magrolimab maintenance dose level. One participant in Part 2 received maintenance dose of 20 mg/kg. Because of confidentiality reason, data for this participant was not provided separately and included in "Magrolimab Priming Dose or Magrolimab 20 mg/kg" arm.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

Participants with checkpoint inhibitor-naive ovarian cancer who previously progressed within 6 months of receiving platinum chemotherapy were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab 45 mg/kg + Avelumab 800 mg (Ovarian Cancer Participants)

Efficacy Analysis Set included checkpoint inhibitor-naive participants with ovarian cancer, who had previously progressed within 6 months of receiving platinum chemotherapy and received at least one dose of magrolimab during this study.

Percentage of Participants With Objective Response (ORR) Assessed by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 in Participants With Ovarian Cancer

Participants with solid tumors were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 or 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) every 2 weeks on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Magrolimab - Part 1 All Participants

All Treated participants in Part 1 were analyzed.

Recommended Phase 2 Dose and Schedule (RP2DS) of Magrolimab in Combination With Avelumab

Pre-dose on Day 1 Cycle 1

1 hour post-magrolimab dose on Day 1 Cycle 1

24 hours post-magrolimab dose on Day 1 Cycle 1

1 hour post-magrolimab dose on Day 8 Cycle 1

24 hours post-magrolimab dose on Day 8 Cycle 1

Pre-dose on Day 22 Cycle 1

Pre-dose on Day 1 Cycle 2

Pre-dose on Day 15 Cycle 2

Pre-dose on Day 1 Cycle 3

Pre-dose on Day 1 Cycle 4

Pre-dose on Day 1 Cycle 5

Pre-dose on Day 1 Cycle 7

Pre-dose on Day 1 Cycle 10

Pre-dose on Day 1 Cycle 11

Pre-dose on Day 1 Cycle 13

Pre-dose on EOT

Pre-dose on Safety Follow-up

Pharmacokinetic Analysis Set (included participants who received any amount of magrolimab with at least one detectable post-treatment serum concentration of magrolimab) with available data in Part 1 were analyzed.

Serum Concentrations of Magrolimab - Safety Run-in (Part 1)

Immunogenicity Analysis Set included participants with at least one reported Anti-Drug Antibody result.

Percentage of Participants With Transient Anti-Drug Antibody to Magrolimab - Safety Run-in (Part 1)

Participants in the Efficacy Analysis Set were analyzed.

Percentage of Participants With Objective Response According to Gynecologic Cancer InterGroup (GCIG) Criteria in Ovarian Cancer

Participants in the Efficacy Analysis Set who achieved objective response according to GCIG criteria. Only 1 participant was analyzed for this Outcome Measure. Data is not reported for participant confidentiality reasons.

Duration of Response (DOR) as Per GCIG Criteria in Participants With Ovarian Cancer

Progression-free Survival (PFS) in Participants With Ovarian Cancer

Participants in the Efficacy Analysis Set were analyzed

Overall Survival (OS) in Participants With Ovarian Cancer

Participants with checkpoint inhibitor-naïve ovarian cancer were treated with starting priming dose of 1 mg/kg of body weight magrolimab IV infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 45 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 11, 15, 22, and 29 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2 and Days 1 and 15 of subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Participants who enrolled in ovarian cancer expansion cohort (Part 2) and for whom paired biopsies were available at both screening and Cycle 3 Day 1 were analyzed.

Percent Change of Immune Cells by Immunohistochemistry in Participants With Ovarian Cancer

Participants with solid tumors were treated with starting priming dose of 1 mg/kg of body weight magrolimab intravenous (IV) infusion (over 3 hours) on Day 1 of Cycle 1 followed by maintenance dose of 30 mg/kg of body weight magrolimab IV infusion (over 2 hours) on Days 8, 15, 22, and 29 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles, in combination with 800 mg avelumab IV infusion (over 1 hour) on Days 8 and 22 of Cycle 1 and Days 1 and 15 of Cycle 2 and subsequent cycles.

Cycle 1 consisted of 35 days and Cycle 2 and subsequent cycle consisted of 28 days. Avelumab was administered 1 hour prior to magrolimab infusion on days when both were given. Treatment was administered until confirmed tumor progression, unacceptable toxicity, clinically significant change in the participant's status that precluded further treatment, voluntary withdrawal, or physician decision.

Spots Global Cancer Trial Database for 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

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Study Description

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