Prostate CancerPhase 2NCT03315871
Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
A Phase 2 study testing Antigen direct immunotherapy: PROSTVAC-V, Antigen direct immunotherapy: PROSTVAC-F and MSB0011359C (M7824) in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Antigen direct immunotherapy: PROSTVAC-V, Antigen direct immunotherapy: PROSTVAC-F and MSB0011359C (M7824)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2018to 4 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathological documentation of prostate cancer confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation. (28 days removed from last systemic therapy, 14 days removed from last radiation therapy).
- Hepatic function eligibility parameters (within 16 days before starting therapy):
- --Bilirubin less than or equal to upper limit of normal (ULN) (OR in participants with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 1.5 times upper limit of normal.
- Adequate renal function defined by an estimated creatinine clearance > 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
- No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses.
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- Willing to travel to the NIH for follow-up visits.
- 18 years of age or older.
- Able to understand and sign informed consent.
- The effects Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) and CV301 on the developing human fetus are unknown. For this reason, men must agree to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) prior to study entry, for the duration of study therapy and at least four months after the last treatment administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
- Additional Inclusion Criteria Specific to Safety Lead-In Cohort
- Castrate testosterone level (<50ng/dl or 1.7nmol /L)
- Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:
- Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer
- OR
- For Biochemical Recurrence:
- Prostate-specific antigen (PSA) progression defined by sequence of rising values separated by >1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Working Group 2 (PCWG2) PSA eligibility criteria). If participants had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For participants on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal.
- --Participants must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >80%).
- Hematological eligibility parameters (within 16 days before starting therapy):
- Granulocyte count greater than or equal to 1000/mm^3
- Platelet count greater than or equal to 100 000/mm^3
- Hemoglobin (Hgb) greater than or equal to 9 g/dL
- Prothrombin time (PT) less than or equal to 1.5 x ULN
- Activated partial thromboplastin time (aPTT) less than or equal to 1.5 x ULN
- Additional Inclusion Criteria Specific to Biochemical Recurrence Cohort
- Biochemical progression defined as follows:
- For participants following definitive radiation therapy: a rise in PSA of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG) -American Society for Therapeutic Radiation Oncology (ASTRO) consensus criteria)
- For participants following radical prostatectomy: rising PSA after surgical procedure (participants must have a PSA greater than or equal to 0.8 ng/mL)
- Participants must have a rising PSA as confirmed by 3 values a minimum of 1 week apart over at least a 1 month period of time.
- Participants must have a PSA doubling time of 5-15 months.
- ECOG performance status of 0-1 (Karnofsky greater than or equal to 80%).
- Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.
- Baseline testosterone greater than or equal to 100 ng/dl.
- PSA less than or equal to 30 ng/mL.
- Hematological eligibility parameters (within 16 days before starting therapy):
- Granulocyte count greater than or equal to 1000/mm3
- Platelet count greater than or equal to 100 000/mm3
- Hgb greater than or equal to 10 g/dL
Who cannot join
- Immunocompromised status due to:
- Human immunodeficiency virus (HIV) positivity.
- Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease.
- Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
- Participants with diabetes type I, vitiligo, or alopecia are allowed.
- Other immunodeficiency diseases
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- Splenectomy
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
- Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days before the first planned dose of investigational therapy. Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
- Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participants ability to carry out the treatment program.
- Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
- History of prior chemotherapy (chemotherapy allowed for lead-in cohort in castration resistant disease.)
- History of prior immunotherapy within the last 3 years (immunotherapy allowed for lead-in cohort in castration resistant disease.)
- Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs.
- Major surgery within 4 weeks prior to enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral Antigen direct immunotherapy's (e.g., vaccinia Antigen direct immunotherapy)
- Previous serious adverse reactions to smallpox vaccination
- History of allergic reactions attributed to monoclonal antibodies (grade 3)
- Known allergy to eggs, egg products, aminoglycoside antibiotics (e.g., gentamicin or tobramycin).
- History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
- Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
- Participants who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to the first planned dose of study drugs), myocardial infarction (< 6 months prior to the first planned dose of study drugs), unstable angina, congestive heart failure (New York Heart Association Classification Class greater than or equal to II), serious cardiac arrhythmia, or uncontrolled hypertension (systolic blood pressure (SBP)>170/diastolic blood pressure (DBP)>105).
- Participants who have received a red cell transfusion within 2 weeks prior to enrollment.
- Participants unwilling to accept blood products as medically indicated.
- Individual tumor lesion(s) in the liver or chest which are 10 cm or larger.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
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.
Read more
Objective:
To see if the combination treatment of PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec vaccinia), CV301, and MSB0011359C (M7824) can induce an anti-tumor impact 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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Antigen direct immunotherapy: PROSTVAC-V, Antigen direct immunotherapy: PROSTVAC-F, MSB0011359C (M7824), Antigen direct immunotherapy: CV301, CT scan of chest
- Keywords
- Antigen direct immunotherapy, PSA, Immunotherapy, Immune Response, Checkpoint Inhibitor
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antigen direct immunotherapy: PROSTVAC-VBiological
Also called rilimogene galvacirepvec/rilimogene glafolivec vaccinia
Recombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection.
Antigen direct immunotherapy: PROSTVAC-FBiological
Also called rilimogene galvacirepvec/rilimogene glafolivec fowlpox
Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection.
MSB0011359C (M7824)Drug
Also called 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.
Antigen direct immunotherapy: CV301Biological
Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.
CT scan of chestDiagnostic test
Also called Computed tomography
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
CT scan of abdomen/pelvisDiagnostic test
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
MRIDiagnostic test
Also called Magnetic resonance imaging
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
PSMADiagnostic test
Also called prostate-specific membrane antigen positron emission tomography scan
Biochemical recurrence group only. Screening, prior to Antigen direct immunotherapy therapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Bone scanDiagnostic test
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
| Study group | Role | What they receive |
|---|---|---|
| 1/Safety Lead-in Combination Therapy (closed December 2018) | Experimental | Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) Receives: Biological: Antigen direct immunotherapy: PROSTVAC-V; Biological: Antigen direct immunotherapy: PROSTVAC-F; Drug: MSB0011359C (M7824); Biological: Antigen direct immunotherapy: CV301; Diagnostic Test: CT scan of chest; Diagnostic Test: CT scan of abdomen/pelvis; Diagnostic Test: MRI; Diagnostic Test: Bone scan |
| 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed) | Experimental | Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) Receives: Biological: Antigen direct immunotherapy: PROSTVAC-V; Biological: Antigen direct immunotherapy: PROSTVAC-F; Drug: MSB0011359C (M7824); Biological: Antigen direct immunotherapy: CV301; Diagnostic Test: CT scan of chest; Diagnostic Test: CT scan of abdomen/pelvis; Diagnostic Test: MRI; Diagnostic Test: PSMA; Diagnostic Test: Bone scan |
| 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance | Experimental | Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 Receives: Biological: Antigen direct immunotherapy: PROSTVAC-V; Biological: Antigen direct immunotherapy: PROSTVAC-F; Biological: Antigen direct immunotherapy: CV301; Diagnostic Test: CT scan of chest; Diagnostic Test: CT scan of abdomen/pelvis; Diagnostic Test: MRI; Diagnostic Test: PSMA; Diagnostic Test: Bone scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Toxicity
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.
Measured: At the end of therapy (7 months)
Prostate Specific Antigen (PSA) Response
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.
Measured: End of treatment (7 months)
Secondary outcomes (2)
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events.
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.
Measured: 6 weeks
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time
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.
Measured: End of treatment after 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start20 Mar 2018
- Primary completion4 Jun 2024
- Study completion4 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ravi A. Madan, M.D., National Cancer Institute (NCI)
- Investigators
- Ravi A Madan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03315871
- Sponsor's protocol ID
- 180005
- Other IDs
- 18-C-0005
- Status last verified
- Jun 2025
- First submitted
- 18 Oct 2017
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (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 the database of Genotypes and Phenotypes (dbGaP).
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
- ClinicalTrials.gov ID
- NCT03315871
- Acronym / sponsor ID
- 180005
- Conditions
- Prostate Cancer
- Keywords
- Antigen direct immunotherapy, PSA, Immunotherapy, Immune Response, Checkpoint Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 20 Mar 2018 (actual)
- Primary completion
- 4 Jun 2024 (actual)
- Study completion
- 4 Jun 2024 (actual)
- First posted
- 20 Oct 2017 (actual)
- Results
- Posted 19 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (rilimogene galvacirepvec/rilimogene glafolivec vaccinia), CV301, and MSB0011359C (M7824) can induce an anti-tumor impact 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1/Safety Lead-in Combination Therapy (closed December 2018) | Experimental | Biological: Antigen direct immunotherapy: PROSTVAC-V, Biological: Antigen direct immunotherapy: PROSTVAC-F, Drug: MSB0011359C (M7824), Biological: Antigen direct immunotherapy: CV301, Diagnostic Test: CT scan of chest, Diagnostic Test: CT scan of abdomen/pelvis, Diagnostic Test: MRI, Diagnostic Test: Bone scanProstvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824) |
| 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed) | Experimental | Biological: Antigen direct immunotherapy: PROSTVAC-V, Biological: Antigen direct immunotherapy: PROSTVAC-F, Drug: MSB0011359C (M7824), Biological: Antigen direct immunotherapy: CV301, Diagnostic Test: CT scan of chest, Diagnostic Test: CT scan of abdomen/pelvis, Diagnostic Test: MRI, Diagnostic Test: PSMA, Diagnostic Test: Bone scanSurveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824) |
| 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance | Experimental | Biological: Antigen direct immunotherapy: PROSTVAC-V, Biological: Antigen direct immunotherapy: PROSTVAC-F, Biological: Antigen direct immunotherapy: CV301, Diagnostic Test: CT scan of chest, Diagnostic Test: CT scan of abdomen/pelvis, Diagnostic Test: MRI, Diagnostic Test: PSMA, Diagnostic Test: Bone scanSurveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Histopathological documentation of prostate cancer confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation. (28 days removed from last systemic therapy, 14 days removed from last radiation therapy).
- Hepatic function eligibility parameters (within 16 days before starting therapy):
- --Bilirubin less than or equal to upper limit of normal (ULN) (OR in participants with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 1.5 times upper limit of normal.
- Adequate renal function defined by an estimated creatinine clearance > 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
Key exclusion criteria (26 listed)
- Immunocompromised status due to:
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
- Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days before the first planned dose of investigational therapy. Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
- Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participants ability to carry out the treatment program.
- Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antigen direct immunotherapy: PROSTVAC-VAlso: rilimogene galvacirepvec/rilimogene glafolivec vacciniaRecombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection. | Biological | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| Antigen direct immunotherapy: PROSTVAC-FAlso: rilimogene galvacirepvec/rilimogene glafolivec fowlpoxRecombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection. | Biological | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| MSB0011359C (M7824)Also: M7824Fully 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. | Drug | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed) |
| Antigen direct immunotherapy: CV301Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously. | Biological | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| CT scan of chestAlso: Computed tomographyScreening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year. | Diagnostic test | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| CT scan of abdomen/pelvisScreening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year. | Diagnostic test | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| MRIAlso: Magnetic resonance imagingScreening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year. | Diagnostic test | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| PSMAAlso: prostate-specific membrane antigen positron emission tomography scanBiochemical recurrence group only. Screening, prior to Antigen direct immunotherapy therapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year. | Diagnostic test | 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
| Bone scanScreening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year. | Diagnostic test | 1/Safety Lead-in Combination Therapy (closed December 2018), 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed), 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance |
Primary outcome
Percentage of Participants With a Toxicity
Time frame: At the end of therapy (7 months)
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.
Prostate Specific Antigen (PSA) Response
Time frame: End of treatment (7 months)
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.
2 secondary outcomes
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events.
Time frame: 6 weeks
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time
Time frame: End of treatment after 7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (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 the database of Genotypes and Phenotypes (dbGaP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi A Madan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Antigen direct immunotherapy: PROSTVAC-V, Antigen direct immunotherapy: PROSTVAC-F and MSB0011359C (M7824) in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With a Toxicity (time frame: At the end of therapy (7 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.