Nivolumab and BMS-986253 for Hormone-Sensitive Prostate Cancer (MAGIC-8)

NCT03689699 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAR7949
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prostate Cancer; Adenocarcinoma of the Prostate

Keywords

Immunotherapy; Nivolumab; BMS-986253; Degarelix; HuMax IL-8

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Prostate-specific Antigen (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.

  Up to 10 months after completion of therapy

• Incidence of Adverse Events That Are Serious in Nature and Related to the Investigational Product.

  All participants receiving at least one dose of the study drug will be evaluated for safety and toxicity. Adverse events will be classified and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 100 days after completion of therapy

Secondary Outcomes (2)

• Percentage Change in PSA

  Baseline, 8 weeks

• Relapse-free Survival (RFS)

  Up to two years

Study Arms (2)

Arm A: Nivolumab alone

EXPERIMENTAL

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).

Drug: Nivolumab; Drug: Degarelix

Arm B: Nivolumab plus BMS-986253

EXPERIMENTAL

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).

Drug: Nivolumab; Drug: Degarelix; Drug: BMS-986253

Interventions

Nivolumab DRUG

A dose of 480mg every 4 weeks as a 30 minute IV infusion for 6 doses has been selected for this study. 6 total doses.

Also known as: Opdivo®

Arm A: Nivolumab alone; Arm B: Nivolumab plus BMS-986253

Degarelix DRUG

Standard treatment at a dose of 240mg subcutaneously (SQ) as a loading dose followed by 80mg SQ every 4 weeks for 4 doses.

Also known as: Firmagon®

Arm A: Nivolumab alone; Arm B: Nivolumab plus BMS-986253

BMS-986253 DRUG

BMS-986253 (also referred to as anti-IL8 mAb or HuMax IL8) is a fully human-sequence IgG1κ monoclonal antibody (mAb) directed against human interleukin-8 (IL-8). Subjects will be treated with an intravenous (IV) flat dose of 2400mg every 2 weeks.

Also known as: HuMax IL-8

Arm B: Nivolumab plus BMS-986253

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented prostatic adenocarcinoma confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen.
• Age ≥18 years
• Previously undergone primary therapy for prostate cancer. Salvage XRT or cryotherapy following primary therapy ≥ 6 months prior to randomization is allowed.
• A rising PSA defined as the following:
• If the subject's primary therapy was RP (radical prostatectomy) (with or without adjuvant or salvage XRT), rising PSA is defined as 2 consecutive rising values above 0.2 ng/mL, each taken ≥ 3 weeks apart, and the last value ≥ 2.0 ng/mL
• If the subject received other primary therapies (e.g. XRT, cryosurgery, brachytherapy), rising PSA is defined per the Phoenix definition, i.e., 2 consecutive rising values above the PSA nadir plus 2.0 ng/mL.
• For the biopsy sub-groups, patients must be willing to undergo pre and on- treatment biopsies.
• PSADT ≤ 12 months. PSADT(prostate-specific antigen doubling time) will be determined from all non-zero PSA values collected preferably, however not limited to, from the 12 months prior to randomization. To calculate PSADT, there must be at least THREE PSA values, with at least 4 weeks between each measurement. The PSADT will be computed from the formula: PSADT = (loge2)/k, with k being the estimated slope of the logarithm of PSA over time. The following web site may also be used: http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)
• Testosterone ≥ 150 ng/dL ≤ 28 days of prior to registration
• Adequate bone marrow, hepatic, and renal function:
• White Blood Cell (WBC)\>3,000 cells/mm3
• Absolute neutrophil count (ANC)\>1,500 cells/mm3
• Hemoglobin \>9.0 g/dL
• Platelet count \>100,000 cells/mm3

You may not qualify if:

• Received any experimental immunotherapy on an experimental clinical trial ≤ 1 year prior to randomization
• PSA \> 50 at time of enrollment
• High volume disease defined as \>5 bone metastases or lymph nodes \>3cm in size.
• Histologic predominance of other types of prostate cancers such as sarcomatous, lymphoma, small cell, and neuroendocrine tumors (note: a maximum of 5 subjects with ductal prostate cancer will be allowed to enroll to each arm of study treatment across all sites).
• Received salvage XRT ≤ 6 months prior to randomization
• Received ADT ≤ 6 months prior to randomization
• Received any form of chemotherapy ≤ 90 days prior to randomization
• Received granulocyte colony-stimulating factor or GM-CSF ≤ 90 days prior to randomization
• Any major surgery requiring general anesthesia ≤ 28 days prior to randomization.
• Any other concurrent or prior treatment for prostate cancer ≤ 28 days prior to randomization.
• An active infection requiring parenteral antibiotic therapy or causing fever (temperature \> 100.5 o F or 38.1 o C) within 1 week prior to randomization
• Prior systemic, ongoing immunosuppressive therapy ≤ 14 days prior to study treatment administration (except for adrenal replacement steroid doses ≤ 10mgdaily prednisone equivalent in the absence of active autoimmune disease or a short course of steroids (\<5 days) up to 7 days prior to initiating study treatment).
• Prior participation in an anti-IL8 clinical study
• A candidate is scheduled or likely to be scheduled for salvage external beam XRT or surgery for prostate cancer during the study period
• Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors such as Dutasteride or Finasteride (prior use of these agents is allowed if ≥3 months prior to randomization).

Sponsors & Collaborators

• Mark Stein: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Sidney Kimmel Cancer Center- Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Nivolumab; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; HuMax-IL8

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Mark N. Stein, MD
• Organization: Columbia University

mns2146@cumc.columbia.edu

212 305 5874

Study Officials

• Mark N. Stein, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: The study will include a total of approximately 30 patients per arm to achieve at least 23 evaluable patients per arm.

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: September 28, 2018
• Study Start: October 11, 2018
• Primary Completion: September 22, 2023
• Study Completion: January 1, 2026
• Last Updated: April 29, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)