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Ovarian CancerPhase 1NCT03558139

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 1 study testing Magrolimab and Avelumab in people with Ovarian Cancer, run by Gilead Sciences at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ovarian Cancer
What is being tested?
Magrolimab and Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
6 sitesUnited States
Study dates
23 May 2018to 3 Dec 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • Individuals with symptomatic or untreated central nervous system (CNS) metastases.
  • Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • University of Chicago

    Chicago, Illinois, 60637

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • START Midwest

    Grand Rapids, Michigan, 49546

  • Oklahoma University Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • South Texas Accelerated Research Therapeutics, LLC

    San Antonio, Texas, 78229

  • University of Washington

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Conditions
Ovarian Cancer
Being tested
Magrolimab, Avelumab
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MagrolimabDrug

    Also called Hu5F9-G4

    Administered intravenously

  • AvelumabDrug

    Also called BAVENCIO®

    Administered intravenously

Study groups in NCT03558139
Study groupRoleWhat they receive
Magrolimab 30 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Avelumab
Magrolimab 45 mg/kg + Avelumab 800 mg (Part 1, Safety Run-in)ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Avelumab
Magrolimab 45 mg/kg + Avelumab 800 mg (Part 2, Ovarian Cancer Expansion)ExperimentalParticipants 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.
Receives: Drug: Magrolimab; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From the first dose date up to 5 weeks

  2. 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.

    Measured: First dose date up to last dose plus 30 days (maximum treatment duration 18.3 months)

  3. 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.

    Measured: 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 outcomes (8)

  1. 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.

    Measured: From the first dose date up to 5 weeks

  2. 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.

    Measured: 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)

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

    Measured: 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.

  4. 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.

    Measured: 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)

  5. 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.

    Measured: 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

  6. 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

    Measured: 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

  7. 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.

    Measured: From first dose date to death or maximum time on study (26.2 months)

  8. 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.

    Measured: Screening and Day 1 Cycle 3 (Cycle 3 duration: 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2018
  2. Study start23 May 2018
  3. Primary completion3 Dec 2020
  4. Study completion3 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03558139
Sponsor's protocol ID
5F9006
Status last verified
Sep 2023
First submitted
30 May 2018
Last updated
1 Apr 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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 Cancer (SITC) Clinical Immuno-Oncology Symposium; 2020 06-08 February. Orlando, FL.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Magrolimab and Avelumab in people with Ovarian Cancer, run by Gilead Sciences at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Safety Run-in (Part 1) (time frame: From the first dose date up to 5 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03558139, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2024.

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