Axatilimab + Olaparib for Breast Cancer

Recruiting at 2 trial locations

Overseen By Filipa Lynce, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: MDS/AML, Pneumonitis, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of axatilimab, a new antibody treatment, combined with olaparib, a standard cancer medication, for individuals with certain types of advanced breast cancer. It specifically targets those with HER2-negative breast cancer linked to BRCA1, BRCA2, or PALB2 gene mutations. The trial seeks participants with HER2-negative breast cancer that has spread or cannot be surgically removed and who have specific gene mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any endocrine therapy at least 7 days before starting the study treatment. Additionally, you cannot take medications that strongly affect certain liver enzymes (CYP450 and CYP3A). It's best to discuss your current medications with the trial team to see if any need to be stopped or adjusted.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that olaparib, a common treatment for breast cancer, usually has manageable side effects with proper care. While side effects occur, they are generally not severe.

Axatilimab, however, is a newer drug under testing, and less information exists about its safety in humans. The trial is in an early stage, aiming to assess its safety when combined with olaparib. This involves determining the best dose that patients can tolerate without serious side effects.

In summary, while many patients can generally manage olaparib, the safety of axatilimab remains under study. This trial is crucial to understanding how well patients can tolerate the combination of both drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Axatilimab and Olaparib for breast cancer because these treatments offer a novel approach compared to current options. Unlike conventional therapies such as chemotherapy, which often target rapidly dividing cells indiscriminately, Olaparib is a PARP inhibitor that specifically targets cancer cells with certain genetic mutations, potentially leading to fewer side effects. Axatilimab is unique as it acts on the immune system, helping to unleash the body's natural defenses against cancer. Together, these treatments could provide a more personalized and effective strategy for tackling breast cancer, especially for patients with specific genetic profiles.

What evidence suggests that the combination of axatilimab and olaparib could be effective for HER2-negative metastatic breast cancer?

Research shows that olaparib, a common treatment for some breast cancers, can slow the progression of cancer in patients with a specific genetic mutation (BRCA-mutated, HER2-negative metastatic breast cancer). In this trial, participants will receive a combination of olaparib and axatilimab, a new drug being tested for its compatibility with olaparib. The goal is for the combination to attack cancer cells more effectively. Although axatilimab remains under study, it might enhance the effects of olaparib. Early results appear promising, but further research is needed to confirm their combined efficacy. ^{1 2 3 4 5}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER2-negative metastatic breast cancer linked to BRCA1/2 or PALB2 mutations. They should have had no more than two prior chemotherapy treatments and must not be candidates for further endocrine therapy if their cancer is hormone receptor positive. Participants need a certain level of blood cells, liver function, and an ECOG performance score of ≤ 2.

Inclusion Criteria

I am willing to have 3 research biopsies.

I had hepatitis C but my viral load is now undetectable.

Participants must agree to use adequate contraception if sexually active with potential to bear children.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to axatilimab or olaparib.

My condition worsened on a PARP inhibitor or within 12 months after taking one.

I have never been treated with a CSF1R antibody.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Window Phase

Predetermined dose of Olaparib 2x daily, taken 12 hours apart for 14 days

2 weeks

1 visit (in-person)

Combination Treatment Phase

Participants receive Axatilimab and Olaparib with tumor biopsies and imaging

Until end of treatment

Days 1 and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 6 months, imaging every 10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab
• Olaparib

Trial Overview The study tests the safety and effectiveness of combining axatilimab (an antibody) with olaparib (a PARP inhibitor), which is already used in treating this type of breast cancer. Axatilimab is new, while olaparib represents standard care.

How Is the Trial Designed?

Group I: Axatilimab + Olaparib Experimental Treatment 2 Interventions

A Bayesian Optimal Interval design will be used to establish the maximum tolerated dose of Axatilimab. Dose reduction and escalation will be per protocol. Participants will complete: * Baseline visit, tumor biopsy, and imaging * Imaging every 8 weeks * Window Phase: --Predetermined dose of Olaparib 2x daily, taken 12 hours apart for 14 days * Combination Treatment Phase: * Cycle 1 through Cycle 2: * Day 1 of 28 day cycle: Tumor biopsy * Days 1 and 15 of 28 day Cycle: Predetermined dose of Axalitimab 1x daily * Days 1 through 28 of 28 day cycle Predetermined dose of Olaparib 2x daily, 12 hours apart * Tumor biopsy after two weeks of Olaparib and at the end of Cycle 2 * Cycle 3 through End of Treatment: * Days 1 and 15 of 28 Day Cycle: Predetermined dose of Axalitimab 1x daily * Predetermined dose of Olaparib 2x daily, taken 12 hours apart * End of Treatment Visit with imaging * Follow Up: Every 6 months for 3 years. Imaging will be every 10 weeks.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

In the phase III OlympiAD trial, olaparib significantly improved progression-free survival (PFS) in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer, with a median PFS of 8.0 months compared to 3.8 months for chemotherapy, indicating a strong efficacy of olaparib.

Subgroup analyses showed consistent benefits of olaparib across various patient characteristics, including hormone receptor status and prior chemotherapy, with higher objective response rates and improved quality of life compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. Senkus, E., Delaloge, S., Domchek, SM., et al.[2023]

In a study involving 34 patients with BRCA1 or BRCA2 mutated metastatic breast cancer, the combination of olaparib and durvalumab demonstrated promising antitumor activity, with 80% of patients showing disease control at 12 weeks.

The treatment was generally safe, with 32% of patients experiencing grade 3 or worse adverse events, but no treatment-related deaths were reported, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek, SM., Postel-Vinay, S., Im, SA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06488378

Phase Ib Study of Axatilimab in Combination With Olaparib ... This research is being done to evaluate the safety and tolerability of the new drug, axatilimab, in combination with olaparib (a standard of care treatment) ...

2. withpower.com withpower.com/trial/phase-1-breast-neoplasms-7-2024-1c6b8

Axatilimab + Olaparib for Breast Cancer Olaparib, a part of the treatment, has shown effectiveness in prolonging progression-free survival in patients with BRCA-mutated, HER2-negative metastatic ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06146

Axatilimab and Olaparib for the Treatment of Patients with ... This phase Ib trial tests the safety, side effects, best dose, and effectiveness of axatilimab and olaparib in treating patients with BRCA 1/2 and PALB2- ...

4. facingourrisk.org facingourrisk.org/research-clinical-trials/study/345/treating-her2-negative-brca12-or-palb2-positive-metastatic-breast-cancer-using-a-new-drug-combined-with-olaparib/printable

Treating HER2-negative, Metastatic Breast Cancer with a ... The study is looking at whether adding a new targeted therapy drug called axatilimab to treatment with the PARP inhibitor olaparib (Lynparza) will improve ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06488378?term=AREA%5BConditionSearch%5D(Breast%20Cancer)%20AND%20AREA%5BBasicSearch%5D(Lynparza)%20AND%20AREA%5BInterventionSearch%5D(olaparib)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=8

Phase Ib Study of Axatilimab in Combination With Olaparib ... The date on which the study sponsor or investigator first submits a study record with summary results information that is consistent with National Library of ...