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Anatomic Stage IV Breast Cancer AJCC v8Phase 1NCT05807126

Testing the Addition of Immunotherapy With Hu5F9-G4 (Magrolimab) to the Usual PARP Inhibitor, Olaparib for Treatment of Metastatic or Recurrent Breast or Castrate-Resistant Prostate Cancer With BRCA Mutations

A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Anatomic Stage IV Breast Cancer AJCC v8 and Castration-Resistant Prostate Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/Ib trial studies the side effects and best dose of Hu5F9-G4 (magrolimab) when given in combination with olaparib for the treatment of patients with breast or castrate-resistant prostate cancer that have spread from where they first started (primary site) to other places in the body (metastatic) or have… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
5 sitesUnited States
Study dates
5 Mar 2024to 6 Dec 2026
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Presence of metastatic and/or recurrent solid tumors (therapy naïve or those with prior therapy) with pathogenic BRCA 1/2 mutated cancers where olaparib is indicated as standard of care therapeutic option (not maintenance) as below:
  • Metastatic breast cancer:
  • Germline - Yes (Y); Somatic - No (N): Must have had prior chemotherapy (chemo) (adjuvant [adj], treatment); or if hormone receptor positive (HR+), must have had prior endocrine therapy or deemed inappropriate for endocrine treatment
  • Metastatic castrate-resistant prostate cancer (CPRC)
  • Germline - Y; Somatic - Y: Treatment after progressive disease on anti-androgens
  • BRCA mutation status must be confirmed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory (lab)
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  • Patients >= 18 years of age. Because no dosing or adverse event data are currently available on the use of Hu5F9-G4 (magrolimab) in combination with olaparib in patients < 18 years of age, children are excluded from this study
  • Patients may not have had prior PARP inhibitor in the metastatic setting when given for therapeutic purposes. Patients with breast cancer who received adjuvant PARP inhibitor (i) are eligible. Patients who had prior maintenance therapy are eligible.
  • At least 4 weeks or 4 prior drug half-lives (whichever is shorter) must have elapsed since completion of the previous systemic therapy
  • Expansion Cohort: Willingness and feasibility to undergo pre and post treatment biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
  • Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
  • Hemoglobin (Hgb) >= 9 g/dL
  • Patients infected with human immunodeficiency virus (HIV) who are on effective anti-retroviral therapy with undetectable viral load within 6 months may be eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with prior brain metastasis that was treated with evidence of resolution or stable disease for 6 months are eligible. Patients are required to be stable and fully tapered off steroids for at least >= 1 month
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Women of child-bearing potential, and men who are sexually active and their partner who may become pregnant, must use contraception during treatment and at least for 6 months (women) and 4 months (men) after the last dose of magrolimab and olaparib. Breastfeeding is not allowed during treatment and for one month after receiving the last dose of therapy
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Who cannot join

  • Previous anti-CD47 therapy
  • Concomitant use of strong CYP3A4 inhibitors/inducers can cause clinically significant drug-interactions; thus, study patients who require the use of these CYP enzymes continuously should be excluded. Study patients need to come off 3 eliminated half-lives of moderate CYP3A4 inhibitors and 5 eliminated half-lives of strong CYP3A4 inhibitors
  • Patients who require immunosuppressive treatments for comorbidities are not eligible
  • Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication
  • Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments
  • Patients who are receiving any other investigational agents
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to magrolimab or other agents used in study
  • Patients with uncontrolled intercurrent illness
  • Pregnant women are excluded from this study because Hu5F9-G4 (magrolimab) is an anti-CD47 monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Hu5F9-G4 (magrolimab), breastfeeding should be discontinued if the mother is treated with Hu5F9-G4 (magrolimab). These potential risks may also apply to other agents used in this study

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: A Phase I/Ib Study of Anti-CD47 Hu5F9-G4 (Magrolimab) in Combination With Olaparib in Patients With BRCA1/2-Mutant Tumors

This phase I/Ib trial studies the side effects and best dose of Hu5F9-G4 (magrolimab) when given in combination with olaparib for the treatment of patients with breast or castrate-resistant prostate cancer that have spread from where they first started (primary site) to other places in the body (metastatic) or have come back after a period of improvement (recurrent) and have mutations in the BRCA1/2 genes. Magrolimab is a monoclonal antibody with potential anticancer activity and the cability to stimulate the immune system and may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Combination therapy with magrolimab and olaparib may be safe and effective in treating BRCA-mutated metastatic or recurrent breast or castrate-resistant prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety, tolerability, toxicity profile (dose-limiting toxicities [DLTs], maximum tolerated doses [MTDs]), and phase 2 recommended dose (P2RD) of Hu5F9-G4 (magrolimab) combined with olaparib.

II. To evaluate the alteration in the immune microenvironment after combination therapy including alteration of specific immune signatures and pathways related to innate immune response and STING pathway. (Dose expansion)

SECONDARY OBJECTIVES:

  1. To evaluate the status of homologous recombination repair (HR)/DNA damage response (DDR) and other genomic mutations.

II. To characterize the pharmacokinetic (PK) profile of olaparib and magrolimab in combination.

EXPLORATORY OBJECTIVES:

  1. To explore the activity of the combination regimen in entire cohort and in the dose expansion cohorts in term of objective response rate (ORR), and progression-free survival (PFS).

II. To evaluate the peripheral immune profile. III. To evaluate alterations in the HR/DDR pathway by circulating tumor (ct)DNA.

IV. To correlate drug exposure with response and/or toxicity.

OUTLINE: This is a dose-escalation study of magrolimab in combination with fixed-dose Olaparib followed by a dose-expansion study.

Patients receive magrolimab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Patients also receive olaparib orally (PO) twice a day (BID) during each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the trial. Patients in the dose-expansion portion of the study also undergo tumor biopsies during screening and on study.

Patients are followed for 30 days after removal from study treatment, and then followed every 12 months for 36 months or until death whichever comes first.

Being tested
Biopsy, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Magrolimab
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsies

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • MagrolimabBiological

    Also called Hu5F9-G4, ONO-7913

    Given IV

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU-0059436

    Given PO

Study groups in NCT05807126
Study groupRoleWhat they receive
Treatment (magrolimab, olaparib)ExperimentalPatients receive magrolimab IV on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Patients also receive olaparib PO BID during each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT and/or MRI throughout the trial. Patients in the dose-expansion portion of the study also undergo tumor biopsies during screening and on study.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Magrolimab; Drug: Olaparib

What is being measured

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

  1. Maximum tolerated dose (MTD) of olaparib with magrolimab (Dose Escalation)

    The MTD is defined as the highest dose level with no more than 1/6 dose-limiting toxicities (DLT). DLT is defined as any grade >= 3 non-hematologic toxicity despite best supportive care or grade >= 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 5.0 attributed as possibly, probably, or definitely related to study drugs during the first cycle of therapy (28 days) lasting more than 7 days.

    Measured: Up to 28 days after the beginning of the treatment cycle

  2. Tumor ribonucleic acid (RNA) sequencing of interferon- gamma (IFN-g) signature, TGF-beta signature, and STING pathway, as well as CD47 expression (Dose Expansion)

    Will be compared between tumor tissue using a non-parametric paired test, at a significance level (alpha) of 0.05. This will only be performed in the expansion cohorts.

    Measured: Baseline and cycle 2 days 1-7

  3. Tumor macrophage infiltrate (Dose Expansion)

    Will be assessed using multiplex immune imaging and their phenotype (M1/M2 ratio) as well as STING pathway activation (TBK1, IRF3 and IFNB protein expression). Will be compared between tumor tissue using a non-parametric paired test, at a significance level (alpha) of 0.05. This will only be performed in the expansion cohorts.

    Measured: Baseline and cycle 2 days 1-7

  4. Tumor infiltrating immune cells (Dose Expansion)

    Will be assessed using multiplex immune imaging. Will be compared between tumor tissue using a non-parametric paired test, at a significance level (alpha) of 0.05. This will only be performed in the expansion cohorts.

    Measured: Baseline and cycle 2 days 1-7

  5. Recommended phase 2 dose (Dose Expansion)

    The RP2D determination will include both the DLT period for the MTD, as well as consideration of later cycle DLTs and the overall safety profile..

    Measured: Up to 28 days after the beginning of the treatment cycle

  6. Incidence of adverse events (Dose Expansion)

    Adverse events will be scored by CTCAE v5.0 and tabulated.

    Measured: Up to 30 days after the last administration

Secondary outcomes (2)

  1. Tumor genomic markers

    Deoxyribonucleic acid (DNA) damage response (DDR) genes including BRCA 1, 2 and other genes such as RAD51C, RAD51D, and PALB, polymorphism status, mutational burden and microsatellite instability (MSI) status will be assessed in available pre-treatment tissue and correlated with immune response by whole exome sequencing.

    Measured: Up to 36 months

  2. Olaparib and magrolimab trough and potentially area under the curve

    Descriptive data will be reported and compared with historical controls.

    Measured: Magrolimab: Cycle 1, day 1 (C1D1): Pre-treatment (Pre); C1D8: Pre, after end of infusion, 1 hour after infusion; C1D15: Pre; Olaparib: C1D1, C1D8, C1D15: Pre

Timeline

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

  1. First posted11 Apr 2023
  2. Study start5 Mar 2024 (estimated)
  3. Primary completion6 Dec 2026 (estimated)
  4. Study completion6 Dec 2026 (estimated)

Why it stopped: No subjects enrolled in the study

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05807126
Sponsor's protocol ID
NCI-2023-02710
Other IDs
NCI-2023-02710, 10551, 10551, UM1CA186690
Status last verified
Apr 2024
First submitted
8 Apr 2023
Last updated
2 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Anatomic Stage IV Breast Cancer AJCC v8 and Castration-Resistant Prostate Carcinoma, run by National Cancer Institute (NCI) at 5 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 25 inclusion and 9 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: withdrawn, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximum tolerated dose (MTD) of olaparib with magrolimab (Dose Escalation) (time frame: Up to 28 days after the beginning of the treatment cycle). The study lists 6 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 NCT05807126.

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 2 May 2024.

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