Axatilimab + Olaparib for Breast Cancer

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

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) in Breast Cancer 1/2 genes (BRCA 1/2) and PALB2 associated HER2-negative metastatic breast cancer. The names of the study drugs involved in this study are: * Axatilimab (a type of antibody) * Olaparib (a type of PARP inhibitor)

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.

What data supports the effectiveness of the drug combination Axatilimab and 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 breast cancer, as compared to standard chemotherapy. It has also demonstrated clinical benefits in high-risk early breast cancer and advanced breast cancer, particularly in patients with specific genetic mutations. ^{1 2 3 4 5}

Is the combination of Axatilimab and Olaparib safe for humans?

Olaparib (Lynparza) has been shown to have a manageable safety profile in breast cancer patients, with side effects that are generally considered manageable. However, specific safety data for the combination of Axatilimab and Olaparib is not available in the provided research. ^{1 2 4 6 7}

How is the drug combination of Axatilimab and Olaparib unique for treating breast cancer?

The combination of Axatilimab and Olaparib is unique because it pairs a novel drug, Axatilimab, with Olaparib, a PARP inhibitor that has shown effectiveness in treating BRCA-mutated, HER2-negative breast cancer. This combination may offer a new approach by potentially enhancing the effectiveness of Olaparib, which is already known to improve progression-free survival in certain breast cancer patients. ^{1 2 3 4 5}

Research Team

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

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, 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

6. England 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. [2021]

7. England 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. [2022]