Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Phase 2

Completed

Conditions: Prostate Cancer

Interventions: Drug: MSB0011359C (M7824)
Diagnostic Test: CT scan of chest
Diagnostic Test: CT scan of abdomen/pelvis
Diagnostic Test: MRI
Diagnostic Test: Bone scan
Diagnostic Test: PSMA

Registration Number: NCT03315871

Lead Sponsor: National Cancer Institute (NCI)

Brief 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. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1/Safety Lead-in Combination Therapy (closed December 2018)	MSB0011359C (M7824)	Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
1/Safety Lead-in Combination Therapy (closed December 2018)	CT scan of chest	Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
1/Safety Lead-in Combination Therapy (closed December 2018)	CT scan of abdomen/pelvis	Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
1/Safety Lead-in Combination Therapy (closed December 2018)	MRI	Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
1/Safety Lead-in Combination Therapy (closed December 2018)	Bone scan	Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	MSB0011359C (M7824)	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	CT scan of chest	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	CT scan of abdomen/pelvis	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	MRI	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	PSMA	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)	Bone scan	Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance	CT scan of chest	Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance	CT scan of abdomen/pelvis	Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance	MRI	Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance	PSMA	Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance	Bone scan	Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Toxicity	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	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1): National Institutes of Health Clinical Center
🇺🇸
Bethesda, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States