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

Anatomic Stage IV Breast Cancer AJCC v8 Clinical Trial

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

Status Withdrawn

Clinical 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 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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. ;

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Castration-Resistant Prostate Carcinoma
• Prostatic Neoplasms
• Stage IVB Prostate Cancer AJCC v8

• NCT number: NCT05807126
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 5, 2024
• Completion date: December 6, 2026