REGN5678 + Cemiplimab for Prostate Cancer

Overseen By Bilal Siddiqui, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: LHRH agonist or antagonist

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 6

Duration: 9 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

A single-center phase Ib/II dose escalation and dose-expansion clinical trial of REGN5678 plus cemiplimab

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like systemic corticosteroids or have received other systemic therapies recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination REGN5678 + Cemiplimab for prostate cancer?

Immune checkpoint inhibitors, like Cemiplimab, have shown promise in treating various cancers by helping the immune system attack cancer cells. However, their success in prostate cancer has been limited, suggesting that careful patient selection might be necessary to identify those who could benefit from such treatments. ^{1 2 3 4 5}

What makes the drug REGN5678 + Cemiplimab unique for prostate cancer?

REGN5678 + Cemiplimab is unique because it combines two different approaches: REGN5678, which may target specific cancer pathways, and Cemiplimab, an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination could offer a novel way to treat prostate cancer by enhancing the body's immune response against the tumor. ^{1 3 5 6 7}

Research Team

Bilal Siddiqui, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for men aged 18+ with advanced prostate cancer (mCRPC) that has worsened after at least two systemic therapies, including anti-androgen therapy. Participants must have adequate organ function, no active infections like HIV or hepatitis, and an ECOG performance status of 0 or 1. They should not be in other trials, have certain other cancers or severe health conditions, and must agree to use contraception.

Inclusion Criteria

My prostate cancer has worsened after two treatments, including a newer hormone therapy.

My blood tests show normal hemoglobin, neutrophil, and platelet levels.

My kidney function is within the normal range.

Exclusion Criteria

Currently receiving treatment in another interventional study

Any medical, psychological or social condition that in the opinion of the investigator, would preclude participation in this study

Has participated in a study of an investigational drug within 4-weeks of first dose of study therapy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-In Phase

Participants receive three weekly doses of REGN5678

3 weeks

3 visits (in-person)

Treatment

Participants transition to every three-week dosing of REGN5678 and cemiplimab

9 months

Visits every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Cemiplimab
• REGN5678

Trial Overview The study tests REGN5678 combined with Cemiplimab in a phase Ib/II trial involving dose escalation and expansion. It's designed to see how well these drugs work together for patients who've already tried multiple treatments for mCRPC.

Participant Groups

Group I: Treatment with REGN5678 Q3W IV + Cemiplimab Q3W IV Experimental Treatment 2 Interventions

Patients will receive three weekly doses of REGN5678 as part of a Lead-In Phase and thentransition to every three-week dosing of the combination of REGN5678 and cemiplimab (anti-PD-1).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

In a study of men with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T, a delayed PSA response was observed, with 19.9% of patients in the PROCEED registry showing a PSA50 response at a median of 5.5 months after treatment.

The median overall survival for patients in the PROCEED cohort was 49 months, suggesting that sipuleucel-T may provide a significant survival benefit despite low immediate response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry. Wei, XX., Kwak, L., Hamid, A., et al.[2022]

Interleukin-6 promotes the expression of the androgen receptor splice variant AR-V7 in prostate cancer, which contributes to resistance against androgen receptor signaling inhibitors (ARSIs).

The combination treatment of the CD105-neutralizing antibody carotuximab with ARSIs showed disease stabilization in 4 out of 9 patients with ARSI-resistant prostate cancer, indicating a potential strategy to overcome resistance by downregulating AR-V7.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit. Smith, BN., Mishra, R., Billet, S., et al.[2023]

In a large registry study involving 1976 patients with metastatic castration-resistant prostate cancer, sipuleucel-T immunotherapy demonstrated a median overall survival of 30.7 months, indicating its potential effectiveness in prolonging life for this patient group.

The treatment was associated with a low incidence of serious adverse events (3.9%) and cerebrovascular events (2.8%), suggesting that sipuleucel-T is a relatively safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Higano, CS., Armstrong, AJ., Sartor, AO., et al.[2021]

The vaccine-based immunotherapy regimen PF-06753512 (PrCa VBIR) demonstrated a safety profile similar to other immune checkpoint inhibitor (ICI) combination trials, with common side effects including fatigue and immune-related thyroid dysfunction in 70.3% of patients.

In patients with biochemical recurrence (BCR), 25.7% achieved a significant decline in PSA levels, indicating modest antitumor activity, while the treatment successfully stimulated antigen-specific immune responses across all patient cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Autio, KA., Higano, CS., Nordquist, L., et al.[2023]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

References

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

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors in Prostate Cancer. [2021]

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

Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry. [2022]

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

Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit. [2023]

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

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). [2023]

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

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]