59 Participants Needed

Nivolumab + BMS-986253 for Prostate Cancer

Recruiting at 4 trial locations
RN
Overseen ByResearch Nurse Navigator
Age: 18+
Sex: Male
Trial Phase: Phase 1 & 2
Sponsor: Mark Stein
Must be taking: LHRH antagonists
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

MAGIC-8 is a two-arm, multicenter, phase 1b/2 study to assess the efficacy of immunotherapy with either Nivolumab (anti-PD-1) or Nivolumab plus BMS-986253 combined with ADT using Degarelix (LHRH antagonist) for men with hormone-sensitive prostate cancer and a rising prostate-specific antigen (PSA). The purpose of this study is to see whether immunotherapy with either Nivolumab alone or Nivolumab plus BMS-986253 combined with Degarelix, which suppresses testosterone, is safe and can decrease the chance that the cancer will come back. The primary objectives are to 1) determine the rate of PSA recurrence defined as a PSA \>0.2ng/ml for radical prostatectomy patients or PSA \>2.0ng/ml for patients who received primary radiation therapy at a time point of 10 months after start of therapy; and 2) determine the safety and tolerability of either nivolumab or nivolumab plus BMS-986253 in combination with degarelix in men with hormone-sensitive prostate cancer. The secondary objectives include determining relapse-free survival (RFS) and % change in PSA to immunotherapy alone.

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 participate if you have received certain treatments like chemotherapy or hormonal therapy recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab + BMS-986253 for prostate cancer?

The research suggests that while single-agent immunotherapies have limited effects on prostate cancer, combination therapies are being explored to improve outcomes. The use of immune checkpoint inhibitors like Nivolumab, which targets the PD-1 pathway, has shown promise in other cancers and may benefit specific groups of prostate cancer patients when combined with other treatments.12345

Is the combination of Nivolumab and BMS-986253 safe for humans?

Nivolumab, used in various cancer treatments, has been associated with side effects like fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects are less common but can include low phosphate levels and low white blood cell counts. Immune-related side effects, where the immune system attacks healthy cells, can also occur.678910

What makes the drug Nivolumab + BMS-986253 unique for prostate cancer?

This drug combination is unique because it targets the IL-8 signaling pathway, which is involved in prostate cancer progression and resistance to other treatments. By blocking IL-8, it may enhance the effectiveness of immune checkpoint inhibitors like Nivolumab, potentially improving immune responses against the cancer.211121314

Research Team

MN

Mark N. Stein, MD

Principal Investigator

Columbia University

Eligibility Criteria

Men over 18 with hormone-sensitive prostate cancer who've had primary therapy like surgery or radiation. They must have rising PSA levels, good physical health (ECOG 0-1 or Karnofsky ≥70%), and normal organ function. Participants need to agree to use contraception for about 7 months post-treatment and be willing to undergo biopsies if in the biopsy subgroup.

Inclusion Criteria

My prostate cancer was confirmed by a biopsy or surgery.
I am 18 years old or older.
I had initial treatment for prostate cancer and any follow-up treatment was over 6 months ago.
See 8 more

Exclusion Criteria

I have a history of HIV or hepatitis B/C.
I have received an organ transplant from another person.
Prior participation in an anti-IL8 clinical study
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab or Nivolumab plus BMS-986253 combined with Degarelix. Nivolumab alone or with BMS-986253 is administered every 4 weeks for 8 weeks, followed by combination with Degarelix every 4 weeks for 16 weeks.

24 weeks
6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for PSA recurrence and adverse events.

10 months

Long-term follow-up

Participants are monitored for relapse-free survival (RFS) and long-term outcomes.

Up to two years

Treatment Details

Interventions

  • BMS-986253
  • Degarelix
  • Nivolumab
Trial OverviewThe MAGIC-8 trial is testing how well Nivolumab alone or combined with BMS-986253 works alongside Degarelix, a testosterone-suppressing drug, in reducing the chance of prostate cancer returning. The study measures PSA recurrence rates at 10 months and checks safety/tolerability.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B: Nivolumab plus BMS-986253Experimental Treatment3 Interventions
Men with hormone-sensitive prostate cancer will receive Nivolumab plus BMS-986253 every 4 weeks for 8 weeks (2 doses), followed by Nivolumab + BMS-986253 + Degarelix every 4 weeks for 16 weeks (4 doses).
Group II: Arm A: Nivolumab aloneExperimental Treatment2 Interventions
Men with hormone-sensitive prostate cancer will receive Nivolumab alone every 4 weeks for 8 weeks (2 doses), followed by Nivolumab + Degarelix every 4 weeks for 16 weeks (4 doses).

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mark Stein

Lead Sponsor

Trials
4
Recruited
150+

Matthew Dallos

Lead Sponsor

Trials
4
Recruited
140+

Bristol-Myers Squibb

Industry Sponsor

Trials
2,731
Recruited
4,127,000+
Headquarters
New York City, USA
Known For
Oncology & Cardiovascular
Top Products
Eliquis, Opdivo, Revlimid, Orencia
Christopher Boerner profile image

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt profile image

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Prostate cancer has a challenging immunosuppressive environment, making it difficult to treat with traditional immunotherapy; currently, sipuleucel-T is the only FDA-approved immunotherapy specifically for prostate cancer, effective mainly for select patients with indolent metastatic castration-resistant prostate cancer.
Future strategies in immuno-oncology for prostate cancer may involve innovative approaches like bispecific antibodies and CAR-T cells targeting specific markers on tumor cells, which could improve patient outcomes by overcoming the immune barriers present in this type of cancer.
Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations.Wong, RL., Yu, EY.[2022]
In a study of 326 prostate adenocarcinoma patients from Spain and Norway, high expression of the immune checkpoint protein B7-H3 was linked to worse outcomes, including biochemical and clinical recurrence, indicating its potential as a target for immunotherapy.
Unlike B7-H3, PD-L1 expression did not show a correlation with clinical outcomes, suggesting that B7-H3 may be a more relevant biomarker for treatment strategies in prostate cancer.
Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer.Nunes-Xavier, CE., Kildal, W., Kleppe, A., et al.[2022]
This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.
Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.
Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis.Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

References

Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. [2022]
Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer. [2022]
Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis. [2022]
Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]
Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer. [2021]
Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]
U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]
Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. [2022]
Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]
Nivolumab Plus Relatlimab: First Approval. [2022]
[Immunotherapy with PD-1 and PD-L1 inhibitors for prostate cancer]. [2021]
Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor). [2023]
Castration-mediated IL-8 promotes myeloid infiltration and prostate cancer progression. [2023]
14.United Statespubmed.ncbi.nlm.nih.gov
Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. [2023]