Cyclophosphamide + Axatilimab + Retifanlimab for Breast Cancer

Overseen By Bora Lim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Interstitial lung disease, Autoimmune disease, Active infections, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of two drugs, cyclophosphamide and axatilimab (an experimental treatment), when combined with a standard dose of retifanlimab for treating metastatic triple-negative breast cancer (TNBC). Researchers are testing these drugs to assess their effectiveness in controlling cancer that has spread and is resistant to standard treatments. The trial targets individuals with TNBC that has either metastasized or recurred and cannot be surgically removed, as well as those with inflammatory breast cancer. Participants must have paused chemotherapy or radiation therapy for at least a week and have a type of breast cancer unresponsive to other treatments. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this new experimental treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must wait at least one week after your last chemotherapy or radiation therapy before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

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

Previous studies have found the combination of axatilimab, retifanlimab, and another drug to be safe and tolerable. Cyclophosphamide, already approved for other uses, has a well-understood safety profile. However, as this is an early-phase trial, the safety of using these drugs together is still under evaluation. Prospective participants should discuss any potential risks with their doctor before joining the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines three agents—Cyclophosphamide, Axatilimab, and Retifanlimab—that target breast cancer differently than standard options like hormone therapy or chemotherapy alone. Axatilimab and Retifanlimab are immune-modulating antibodies that help the body’s immune system identify and attack cancer cells more effectively. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, this combination aims to enhance specific immune responses, potentially improving effectiveness and reducing side effects. This innovative approach could offer new hope for patients by potentially delivering more precise and powerful treatment.

What evidence suggests that this trial's treatments could be effective for metastatic TNBC?

Research has shown that blocking PD-1/PD-L1, as the drug Retifanlimab does, can benefit some breast cancer patients when combined with other treatments. Cyclophosphamide, a chemotherapy drug, has long been used to treat various cancers by killing cancer cells. Axatilimab targets specific immune cells to help fight cancer by reducing inflammation. This trial studies the combination of Cyclophosphamide, Axatilimab, and Retifanlimab to determine if they work better together in treating metastatic triple negative breast cancer (TNBC). Early results suggest that such combinations may enhance treatment effectiveness for patients with this type of breast cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Bora Lim, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic Triple Negative Breast Cancer (TNBC). Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and have no conflicting conditions.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.

Has at least one measurable lesion per RECIST 1.1

Exclusion Criteria

I have recovered from side effects of previous cancer treatments, except for hair loss.

I have had interstitial lung disease or non-infectious pneumonitis.

I haven't taken high-dose steroids or immunosuppressants for autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of cyclophosphamide, axatilimab, and retifanlimab to determine the best dose for metastatic TNBC

12 months

Regular visits for medication diary review and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab
• Cyclophosphamide
• Retifanlimab

Trial Overview The study aims to determine the optimal doses of cyclophosphamide and axatilimab when combined with a standard dose of retifanlimab in treating TNBC. It's a Phase Ib/II trial, which means it's partly about finding the right dose (Phase Ib) and partly about testing effectiveness (Phase II).

How Is the Trial Designed?

Group I: Treatment with Cyclophosphamide + Axatilimab + Retifanlimab Experimental Treatment 3 Interventions

Participants will be requestd to maintain a medication diary of each dose of medication while taking oral cyclophosphamide. The medication diary will be returned to clinic staff at the end of each course.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Adjuvant therapies, particularly those containing anthracycline/cyclophosphamide (AC), significantly improve disease-free and overall survival in breast cancer patients, with AC regimens showing an 11% greater reduction in the risk of death compared to non-AC regimens.

Tamoxifen effectively reduces recurrence and death in patients with estrogen receptor-positive tumors, and its combination with chemotherapy further enhances survival, while ongoing trials are investigating the potential benefits of adding trastuzumab for HER2-positive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in the adjuvant treatment of breast cancer: the role of trastuzumab. Smith, I.[2020]

Anti-PD-1 and anti-PD-L1 antibodies show modest response rates as standalone treatments for metastatic breast cancer, but they are generally well tolerated and can provide significant, lasting benefits for some patients.

These antibodies can be safely combined with various systemic therapies, including chemotherapy and targeted therapies, as well as radiotherapy, suggesting potential for enhanced effectiveness in treating metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer. Page, DB., Bear, H., Prabhakaran, S., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-2-breast-neoplasms-9-2025-72f18

Cyclophosphamide + Axatilimab + Retifanlimab for Breast ... Research shows that drugs blocking PD-1/PD-L1, like Retifanlimab, can provide significant benefits in some breast cancer patients when combined with other ...

2. trial.medpath.com trial.medpath.com/clinical-trial/8c115f5bcdded69e/nct06959537-cyclophosphamide-axatilimab-retifanlimab-tnbc

A Phase Ib Study of Novel Combination (New) of Low Dose ... The goal of this clinical research study is to find the best dose of the drugs cyclophosphamide and axatilimab that can be given in combination with the ...

3. onclive.com onclive.com/view/insights-into-real-world-evidence-in-chronic-gvhd

Insights Into Real-World Evidence in Chronic GVHD Panelists discuss how real-world evidence shows lower response rates and shorter time to next treatment compared to clinical trials due to more ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06320405?term=SNDX&rank=7

Study Details | NCT06320405 | Axatilimab in Combination ... This phase I/II trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-1-2-ib-ii-novel-combination-new-low-dose-oral-cyclophosphamide-s-trial-nct06959537

A Phase Ib Study of Novel Combination (New) of Low Dose ... A Study of Low-Dose Cyclophosphamide Combined with Axatilimab and Retifanlimab in Treating Metastatic Triple Negative Breast Cancer. Check your eligibility

6. onclive.com onclive.com/view/safety-and-efficacy-of-axatilimab-at-3-different-doses-in-patients-with-chronic-graft-versus-host-disease-agave-201-

Safety and Efficacy of Axatilimab at 3 Different Doses in ... Karolina Faysman, RN, MSN, AOCNP, DNPc, highlights efficacy, safety, and patient-reported outcomes from the phase 2 AGAVE-201 trial ...