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

Prostate cancer is common and remains a major cause of death in men. Following local therapy
with surgery or radiation, a significant number of men recur either with a rising PSA only
(biochemical recurrence (BCR)) or clear metastatic disease on imaging. Although androgen
deprivation therapy (ADT) is a frequently used and effective treatment for prostate cancer,
it is associated with significant side effects including fatigue, hot flashes, decreased
libido and bone loss. Therefore, new approaches to decrease the time on ADT are crucial to
improving quality of life for men with prostate cancer.

Once initiated, ADT can be given either continuously or intermittently. However, even with an
intermittent approach the ADT-free interval typically decreases with each cycle and most men
eventually develop castration resistance. Therefore new treatment strategies are needed to
improve disease control while minimizing ADT exposure for men with early prostate cancer.

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