Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Brief Summary

Detailed Description

Background: Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy (i.e., biochemically recurrent \[BCR\] prostate cancer). The primary goal in these patients is to prevent morbidity from their cancer that results from disease progression and metastatic disease on conventional imaging. ADT can lower the prostate-specific antigen (PSA) in these patients, but because of its substantial side effect profile and ambiguous long-term impact, it is generally deferred by most patients until there is a rapid escalation in their PSA. Immunotherapy presents an alternative option for these patients that is especially attractive because it is not associated with substantial toxicity. Also, since immunotherapy can have lasting effects after treatment due to a sustained activated immune response, patients will not be required to take these treatments indefinitely to potentially benefit clinically. Current and previous clinical trials have demonstrated that single agent immunotherapy can impact PSA in patients in this population. The focus of this study is to determine if combination immunotherapy with Antigen direct immunotherapy antigen directed immunotherapy can initiate an immune response in the first 4 months that is then augmented by an immune checkpoint inhibitor in the following 3 months. In addition to PSA responses (the primary metric in this population), safety, changes in immune responses, and PSA kinetics will also be evaluated. Objectives: Primary Objectives: Safety Lead-In: To evaluate the safety and tolerability of combination immunotherapy in participants with castration-resistant prostate cancer Biochemical Recurrence: To determine if the combination immunotherapy can induce a 30% decline in PSA in 28% of participants with biochemically recurrent prostate cancer. Eligibility Criteria (for biochemical recurrence): Histologically confirmed adenocarcinoma of the prostate Participants with negative computed tomography (CT) Scan and Tc-99m Bone Scan Participants with a PSA over 0.8 ng/ml for participants following radical prostatectomy or for participants following definitive radiation therapy: a rise in PSA of \>= 2 ng/mL above the nadir Participants with a PSA doubling time of 5-15 months No history of active autoimmune disease or history of organ compromising autoimmune disease Eastern Cooperative Oncology Group (ECOG) 0-1 Safety lead-in cohort will evaluate 6 participants with castration resistant prostate cancer Design: Three-arm, non-randomized study Accrual goal is a total of 37 evaluable participants (6 in an initial safety cohort, 6 participants who received M7824 (MSB0011359C) as part of the initial investigation and 25 homogenously treated participants without M7824) to evaluate response Participants from a previous study (NCT02649439) with nearly identical eligibility can serve as a contemporary control for secondary endpoints Following the safety lead-in, all participants will be enrolled and may undergo a surveillance period during which up to 4 consecutive monthly PSA values will be captured by the labs. After surveillance period, if applicable, participants will be treated with 2 Antigen direct immunotherapy's concurrently, Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) and CV301, during months 1-4. For months 5-7, MSB0011359C \[an anti-programmed Cell Death Ligand 1 (PD-L1) antibody (avelumab) with TGF(Beta)-Trap molecule\] will be added to the regimen. -Effective with amendment v7/29/2021, MSB0011359C (M7824) will no longer be given as part of the treatment combination for the Biochemical Recurrence cohort (Arms 3) Participants will be monitored for on-treatment and post-treatment PSA, immune and imaging responses.

Primary Outcomes

Secondary Outcomes

• Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events.(6 weeks)
• Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time(End of treatment after 7 months)