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Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

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

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
59 participants (actual)
Sponsor
Mark Stein · Other
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
11 Oct 2018
Primary completion
22 Sept 2023
Completion
2 May 2024
First posted
28 Sept 2018
Last update posted
15 Oct 2026
Conditions
Prostate Cancer · Adenocarcinoma of the Prostate

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2018202020222024
  1. Ph 1/2

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

    NCT03689699

    11 Oct 2018 to 2 May 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • NivolumabDrug
  • DegarelixDrug
  • BMS-986253Drug

Arms2

  • Experimental

    Arm A: Nivolumab alone

    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).

  • Experimental

    Arm B: Nivolumab plus BMS-986253

    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).

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Number of Participants With Prostate-specific Antigen (PSA) Recurrence

    Time frame · Up to 10 months after completion of therapy, an average of 15 months

    Registry description

    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.

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

    Time frame · Up to 10 months after completion of therapy, an average of 15 months

    Registry description

    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.

Secondary outcomes(2)
  1. Percentage Change in PSA

    Time frame · Baseline, 8 weeks

    Registry description

    Determine the % change in PSA in response to immunotherapy by comparing the PSA prior to and following 8 weeks of immunotherapy and before initiation of ADT

  2. Relapse-free Survival (RFS)

    Time frame · Up to two years

    Registry description

    Relapse-free survival (RFS) is the length of time after primary cancer treatment ends that a patient survives without any signs or symptoms of that cancer. "Relapse" is defined as a PSA \>0.2ng/ml for radical prostatectomy patients or PSA \>2.0ng/ml for patients who received primary radiation therapy.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Up to 10 months after completion of therapy, an average of 15 months

Number of Participants With Prostate-specific Antigen (PSA) Recurrence

GroupValue (Participants)
Arm A: Nivolumab Alone8
Arm B: Nivolumab Plus BMS-9862536
Primary outcomeCount of participants· Up to 10 months after completion of therapy, an average of 15 months

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

GroupValue (Participants)
Arm A: Nivolumab Alone4
Arm B: Nivolumab Plus BMS-9862533
Secondary and other outcome results(2)
Secondary outcomeMedian· Baseline, 8 weeks

Percentage Change in PSA

GroupValue (percent decline from baseline)
Arm A: Nivolumab Alone95.5
Arm B: Nivolumab Plus BMS-98625397.3
Secondary outcomeMedian· Up to two years

Relapse-free Survival (RFS)

GroupValue (months)
Arm A: Nivolumab Alone12.5
Arm B: Nivolumab Plus BMS-98625312.0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Arm A: Nivolumab AloneMen 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).0 / 304 / 3029 / 30
Arm B: Nivolumab Plus BMS-986253Men 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).0 / 293 / 2929 / 29

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Male
Age
from 18 Years up to 99 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 * Serum creatinine \<1.5 × upper limit of normal (ULN) * Serum total bilirubin \<1.5 × ULN * ALT (alanine aminotransferase) \<3 × ULN * AST(aspartate aminotransferase) \<3 × ULN * Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent) * Willingness to use barrier contraception during treatment plus 5 half-lives of nivolumab (\~125 days) plus 90 days (duration of sperm turnover) for a total of 215 days post-treatment completion (azoospermic men are not exempt from contraceptive requirements) Exclusion Criteria: 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). * 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

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