Cyclophosphamide + Axatilimab + Retifanlimab for Breast Cancer

Overseen By Bora Lim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Trial Summary

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.

What data supports the effectiveness of the drugs Axatilimab, Cyclophosphamide, and Retifanlimab for breast cancer?

Research shows that drugs blocking PD-1/PD-L1, like Retifanlimab, can provide significant benefits in some breast cancer patients when combined with other treatments. Cyclophosphamide, part of several successful chemotherapy regimens, has been shown to improve survival in breast cancer patients when used with other drugs. ^{1 2 3 4 5}

Is the combination of Cyclophosphamide, Axatilimab, and Retifanlimab safe for humans?

Cyclophosphamide has been used in various chemotherapy combinations for breast cancer and is generally considered safe, though it can have side effects like nausea and low blood cell counts. Retifanlimab, a PD-1 inhibitor, is part of a class of drugs used in breast cancer treatment, and while generally safe, it can cause immune-related side effects. There is no specific safety data available for Axatilimab in breast cancer, but it is important to discuss potential risks with your doctor. ^{2 6 7 8 9}

How is the drug combination of Cyclophosphamide, Axatilimab, and Retifanlimab unique for breast cancer treatment?

This drug combination is unique because it combines Cyclophosphamide, which can deplete regulatory T cells (immune cells that suppress the body's immune response), with Axatilimab and Retifanlimab, which are likely to enhance the immune system's ability to fight cancer. This approach aims to improve the effectiveness of immunotherapy in breast cancer by targeting both the tumor and the immune environment. ^{2 10 11 12 13}

What is the purpose of this trial?

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 standard dose of retifanlimab to patients with metastatic TNBC.

Research Team

Bora Lim, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

References

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

Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[Current status in the treatment of breast cancer. II. Adjuvant chemotherapy, palliative polychemotherapy, chemoimmunotherapy--rating and results (author's transl)]. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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

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

The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: a post hoc analysis of the IBIS 3 trial. [2022]

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

Meta-analysis of adjuvant cyclophosphamide/methotrexate/5-fluorouracil chemotherapy in postmenopausal women with estrogen receptor-positive, node-positive breast cancer. [2013]

6. China pubmed.ncbi.nlm.nih.gov

The efficacy and safety of PD-1/PD-L1 inhibitors in breast cancer: a systematic review and meta-analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Immunotherapy for early breast cancer: too soon, too superficial, or just right? [2021]

8. England pubmed.ncbi.nlm.nih.gov

A randomized phase II study comparing capecitabine alone with capecitabine and oral cyclophosphamide in patients with advanced breast cancer-cyclox II. [2023]

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

Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast cancer. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer. [2023]

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

Immunostimulatory and anti-tumor metronomic cyclophosphamide regimens assessed in primary orthotopic and metastatic murine breast cancer. [2023]