Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Vaccines

Immunomodulating Agents

Immunoglobulins

Surveillance followed by Prostvac + CV301 then Prostvac + CV301 + MSB0011359C

Surveillance as needed followed by Prostvac + CV301

Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection.

PROSTVAC-V

Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection.

PROSTVAC-F

Fully human bifunctional fusion protein that combines IgG1 anti-PD-L1 and TGFbetaRII as a monoclonal antibody. Administered via IV infusion over 1 hour.

MSB0011359C (M7824)

Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.

CV301

Ravi A Madan, M.D.

Background:

Some people with prostate cancer have a rise in prostate-specific antigen (PSA). This can happen even after treatments like radiation and surgery. Androgen deprivation therapy (ADT) drugs and close monitoring are one standard way to treat this group of people. Another way is to monitor people and their PSA values over time. Researchers want to see if a combination of new drugs can help these people.

Objective:

To see if the combination treatment of PROSTVAC, CV301, and MSB0011359C (M7824) can induce an anti-tumor attack in people with biochemically recurrent prostate cancer.

Eligibility:

People ages 18 and older with certain kinds of prostate cancer

Design:

Participants will be screened with

* Medical history
* Physical exam
* Blood and urine tests
* A scan of the neck, chest, abdomen, and pelvis
* A bone scan

A sample of tissue that was already taken will be tested. This will confirm the diagnosis, stage, and disease status.

Some participants will have close monitoring with four monthly PSA checks.

All participants will get two study drugs as shots under the skin. They will get the third drug in a vein. They will get the drugs over at least 7 months. Their vital signs will be checked before they get the drugs and for up to 1 hour after.

Participants will have frequent study visits. They will have physical exams, urine and blood tests, and scans.

Participants will return to the clinic about 4 weeks after they stop taking the study drugs. They will have a medical history, physical exam, and blood tests. They may also have long-term follow-up visits.

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 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 immune-cell mobilizing vaccines 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 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

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 as part of the initial investigation and 25 homogenously treated participants) to evaluate response

Participants from an on-going 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 vaccines concurrently, Prostvac and CV301, during months 1-4. For months 5-7, MSB0011359C \[an anti-PD-L1 antibody (avelumab) with TGF(Beta)-Trap molecule\] will be added to the regimen.

-Effective with amendment v7/29/2021, MSB0011359C will no longer be given as part of the treatment combination for the Biochemical Recurrence cohort (Arms 2 and 3)

Participants will be monitored for on-treatment and post-treatment PSA, immune and imaging responses.

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

fraction of evaluable subjects who experience at least a 30% decline from the maximum to the minimum PSA value while on study

The slopes obtained after administering the vaccines alone or in combination with the checkpoint inhibitor will be tested vs the slopes obtained prior to administering the vaccines, using a two-tailed 0.05 significance level paired t-test or Wilcoxon signed rank test (if the paired differences are not normally distributed)

Reprting the grade of adverse events noted in each participant and reporting the fraction with grade 3 and grade 4 adverse events

Spots Global Cancer Trial Database for msb0011359c (m7824)