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

• Status: Recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: Male

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-sepcific 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charles G. Drake; Matthew Dallos
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Hormones; Nivolumab

Criteria

Inclusion Criteria:

• Age ≥18 years.

• Histologically confirmed adenocarcinoma of the prostate.

• Previously undergone primary therapy for prostate cancer (radical prostatectomy (RP) or external beam radiation (XRT) or RP + XRT). Salvage XRT following RP ≥ 6 months prior to registration is allowed.

• Rising PSA (two consecutive values ≥2.0 ng/mL above the PSA nadir taken ≥3 weeks apart). PSA level of 2-25 ng/mL (PSA up to 50 is allowed for patients undergoing pre- and on-treatment biopsies).

• For the biopsy sub-groups, subjects must be willing to undergo pre- and on-treatment biopsies.

• PSA Doubling Time (PSADT) ≤12 months

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or Karnofsky score ≥70.

• Adequate bone marrow, hepatic, and renal function.

• Willingness to use barrier contraception during treatment.

• Willingness to provide written informed consent and HIPAA authorization.

Exclusion Criteria:

• Received any experimental immunotherapy on an experimental clinical trial ≤ 1 year prior to registration.

• PSA > 25 at time of enrollment (or PSA >50 for patients receiving pre- and on-treatment biopsies).

• Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors

• Received salvage XRT ≤ 6 months prior to registration

• Received ADT ≤ 6 months prior to registration

• Received any form of chemotherapy ≤ 90 days prior to registration

• Received granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor (GM-CSF) ≤ 90 days prior to registration

• Any major surgery requiring general anesthesia ≤ 28 days prior to registration.

• Any other concurrent or prior treatment for prostate cancer ≤ 28 days prior to registration.

• An active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 F or 38.1 C) within 1 week prior to registration.

• Prior systemic, ongoing immunosuppressive therapy ≤ 14 days prior to study treatment administration (except for adrenal replacement steroid doses ≤ 10mg daily 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 use of experimental agents for prostate cancer

• Prior participation in an anti-interleukin 8 (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 (prior use of these agents is allowed if ≥3 months prior to registration).

• History of known or suspected autoimmune disease with the following exceptions:

• Asthma and/or allergic rhinitis (seasonal allergies)

• Vitiligo

• Resolved childhood atopic dermatitis

• Psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.

• Residual hypothyroidism due to an autoimmune condition only requiring hormone replacement

• Euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin (Ig) prior to the first dose of study treatment).

• Type 1 diabetes mellitus

• History of malignancy within the last 2 years (except non-melanoma skin cancers and superficial bladder cancer) and for which no additional therapy is required or anticipated to be required during the study period.

• Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate

• Known prior or current history of HIV and/or hepatitis B/C

• Prior organ allograft