Trial Outcomes & Findings for Combination Immunotherapy in Biochemically Recurrent Prostate Cancer (NCT NCT03315871)

Last Updated: 2025-06-19

Results Overview

Percentage of participants with a toxicity assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

At the end of therapy (7 months)

Results posted on

2025-06-19

Participant Flow

Participant milestones

Participant milestones
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.
Safety Lead-In STARTED	6	0	0
Safety Lead-In COMPLETED	6	0	0
Safety Lead-In NOT COMPLETED	0	0	0
PROSTVAC + CV301 + M7824 STARTED	0	8	0
PROSTVAC + CV301 + M7824 COMPLETED	0	2	0
PROSTVAC + CV301 + M7824 NOT COMPLETED	0	6	0
PROSTVAC + CV301 STARTED	0	0	26
PROSTVAC + CV301 COMPLETED	0	0	24
PROSTVAC + CV301 NOT COMPLETED	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.
PROSTVAC + CV301 + M7824 Withdrawal by Subject	2	0
PROSTVAC + CV301 + M7824 Adverse Event	2	0
PROSTVAC + CV301 + M7824 Physician Decision	1	0
PROSTVAC + CV301 + M7824 Participant came off study for intercurrent medical illness.	1	0
PROSTVAC + CV301 Progressive disease	0	1
PROSTVAC + CV301 An unrelated lymphoma diagnosis requiring therapy	0	1

Baseline Characteristics

Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=8 Participants Surveillance as defined by the protocol followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=26 Participants Surveillance as defined by the protocol followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=93 Participants	2 Participants n=4 Participants	7 Participants n=27 Participants	11 Participants n=483 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants	6 Participants n=4 Participants	19 Participants n=27 Participants	29 Participants n=483 Participants
Age, Continuous	64.5 years STANDARD_DEVIATION 5.37 • n=93 Participants	74.41 years STANDARD_DEVIATION 8.38 • n=4 Participants	69.22 years STANDARD_DEVIATION 6.61 • n=27 Participants	69.55 years STANDARD_DEVIATION 7.29 • n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	8 Participants n=4 Participants	26 Participants n=27 Participants	40 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=93 Participants	8 Participants n=4 Participants	24 Participants n=27 Participants	37 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants	5 Participants n=483 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	7 Participants n=4 Participants	22 Participants n=27 Participants	34 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Region of Enrollment United States	6 participants n=93 Participants	8 participants n=4 Participants	26 participants n=27 Participants	40 participants n=483 Participants

PRIMARY outcome

Timeframe: At the end of therapy (7 months)

Outcome measures

Outcome measures
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=8 Participants Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=26 Participants Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
Percentage of Participants With a Toxicity	6 Percentage of participants	7 Percentage of participants	24 Percentage of participants

PRIMARY outcome

Timeframe: End of treatment (7 months)

Population: 8/40 participants enrolled were not analyzed because they were not evaluable.

Proportion of evaluable participants who experience at least a 30% decline. PSA is a tumor marker in prostate cancer and elevated in participants with this stage of disease. Declines of 30% can be associated with favorable clinical outcomes.

Outcome measures

Outcome measures
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=2 Participants Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=24 Participants Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
Prostate Specific Antigen (PSA) Response	0 Proportion of participants	0 Proportion of participants	0 Proportion of participants

SECONDARY outcome

Timeframe: 6 weeks

Number of participants with related and/or unrelated Grade 3 and Grade 4 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Reporting the grade of adverse events noted in each participant and reporting the fraction with grade 3 and grade 4 adverse events.

Outcome measures

Outcome measures
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=8 Participants Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=26 Participants Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events. Grade 3 Unrelated	1 Participants	2 Participants	3 Participants
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events. Grade 4 Unrelated	0 Participants	0 Participants	0 Participants
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events. Grade 3 Related	1 Participants	1 Participants	0 Participants
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events. Grade 4 Related	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: End of treatment after 7 months

Population: The protocol does not pre-specify to only collect and assess this Outcome Measure in safety 1/Lead-In Cohort. Castration-resistant prostate cancer (CRPC) participants in the safety 1/Lead-In Cohort were evaluated for safety \& PSA changes. PSA DT is not a relevant clinical parameter in CRPC disease state, therefore that data was not evaluated for this outcome. Beyond safety CRPC participants will only be evaluated in a descriptive manner, which was done with PSA responses in outcome measure#2.

PSA Doubling Time (DT) is the time interval (measured in months) it takes for PSA levels to double. PSA DT was calculated using the Memorial Sloan Kettering online PSA Doubling Time calculator. A long PSA DT suggests more indolent disease based on published data. PSA doubling time has been associated with better clinical outcomes in BCR. Note that PSA DT is calculated on a per participant basis and thus will be presented as number of evaluable participants with a change in PSA DT. A change in 20% would be considered meaningful and not due to lab variations. Thus, the data for this outcome is presented as number of evaluable participants experiencing a 20% change in PSA DT.

Outcome measures

Outcome measures
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=8 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=26 Participants Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time Participants evaluable for change in PSA Doubling Time	2 Participants	23 Participants	—
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time Participants with greater than 20% increase in PSA Doubling Time	1 Participants	11 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 Participants Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=8 Participants Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=26 Participants Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	6 Participants	7 Participants	25 Participants

Adverse Events

1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018]

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021]

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1/ Lead-In Cohort (Closed December 2018)/Arm 1/Combination Therapy [Closed December 2018] n=6 participants at risk Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm 1/Combination Therapy [Closed March 2021] n=8 participants at risk Surveillance followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. MSB0011359C (M7824): Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.	2/Biochemical Recurrence Cohort/Arm2/Combo Therapy (Tx)+/Arm3/Combo Antigen Direct Immunotherapy n=26 participants at risk Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 PROSTVAC-V: Recombinant vaccinia virus vector Antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. PROSTVAC-F: Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. CV301: Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/8 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	3.8% 1/26 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Investigations CPK increased	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 2 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Cardiac disorders Cardiac disorders - Other, specify: Accelerated Junctional Rhythm	16.7% 1/6 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/8 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Diverticulitis	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/8 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	3.8% 1/26 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Infections and infestations Infections and infestations - Other, specify: Covid	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Cardiac disorders Myocarditis	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 2 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Lymphoma	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/8 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	3.8% 1/26 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Nervous system disorders Stroke	0.00% 0/6 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.	0.00% 0/26 • All-Cause Mortality was monitored/assessed for an average of 32 days. Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.

Other adverse events

Additional Information

Dr. Ravi A. Madan

National Cancer Institute

Phone: 301-480-7168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place