Combination Immunotherapy for Prostate Cancer

Overseen By Willie C Jackson

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Androgen deprivation therapy

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: HIV, Autoimmune diseases, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of new drugs to determine if they can produce an anti-tumor effect in individuals with recurrent prostate cancer, specifically when PSA levels rise after initial treatment. The trial administers PROSTVAC (a cancer vaccine), CV301 (another cancer vaccine), and MSB0011359C (M7824, an experimental immunotherapy drug) through shots and IVs to assess their effectiveness in managing the cancer. Suitable candidates have prostate cancer with rising PSA levels following treatments like surgery or radiation. Participants must travel for regular check-ups and monitoring. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you continue androgen deprivation therapy (ADT) if you are on it. Some medications, like those for urinary symptoms or certain corticosteroids, are not allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies found CV301 to be safe when used alone or with other treatments, with no major safety issues reported. Research has shown that MSB0011359C (M7824) also has a manageable safety profile, indicating that while some side effects may occur, they are usually not severe and can be managed. Studies have indicated that PROSTVAC, another drug in the combination, was safe and well-tolerated, though it did not significantly extend life in some cases. Overall, this information suggests that the combination of these drugs in the trial is likely safe for participants. The trial is in Phase 2, meaning earlier stages have tested the treatment's safety. Always consult the trial team for more details and personal advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they combine immunotherapy agents that may boost the body's own ability to fight cancer. Unlike standard treatments like hormone therapy or chemotherapy, these investigational treatments utilize vaccines like PROSTVAC and CV301 to target and train the immune system specifically against cancer cells. Another unique feature is the inclusion of M7824, a bifunctional fusion protein that blocks two pathways often used by cancer to escape immune detection. This combination approach has the potential to improve the immune response against prostate cancer, offering a new hope for patients who have experienced biochemical recurrence.

What evidence suggests that this trial's combination immunotherapy treatments could be effective for prostate cancer?

Research has shown that PROSTVAC, one of the treatments in this trial, yields promising results in extending life expectancy. Specifically, it increased the average survival time by 8.5 months for men with advanced prostate cancer compared to those who received a placebo. Additionally, studies on M7824 (MSB0011359C), another treatment option in this trial, have demonstrated positive effects, including instances where cancer completely disappeared. Early evidence suggests that a decrease in PSA levels, a marker used to monitor prostate cancer, correlates with better outcomes. These findings indicate that the combination therapy tested in this trial could have a strong effect against tumors in prostate cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Men aged 18+ with specific prostate cancer types, who've had a rise in PSA after treatments like surgery or radiation. They must agree to use effective contraception and have no other active cancers or life-threatening illnesses. Participants should not have received certain therapies recently and must be willing to travel for follow-up visits.

Inclusion Criteria

I am fully active or can carry out light work.

Negative CT scan/MRI and bone scan for metastatic prostate cancer.

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.

Exclusion Criteria

- Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participant's ability to carry out the treatment program.

I am not taking medications like finasteride or saw palmetto that affect PSA levels.

You are allergic to eggs or certain antibiotics like gentamicin or tobramycin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surveillance

Participants undergo a surveillance period with up to 4 consecutive monthly PSA values captured

4 months

4 visits (in-person)

Treatment

Participants receive Prostvac and CV301 vaccines concurrently for 4 months, followed by MSB0011359C for 3 months

7 months

Frequent visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants may have long-term follow-up visits to monitor PSA and immune responses

What Are the Treatments Tested in This Trial?

Interventions

• CV301
• MSB0011359C (M7824)
• PROSTVAC-F
• PROSTVAC-V

Trial Overview The trial tests if the combination of PROSTVAC, CV301, and MSB0011359C (M7824) can trigger an anti-tumor response in patients with biochemically recurrent prostate cancer. Patients will receive these drugs over at least 7 months and undergo regular monitoring including blood tests, scans, and physical exams.

How Is the Trial Designed?

Group I: 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance Experimental Treatment 8 Interventions

Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301

Group II: 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed) Experimental Treatment 9 Interventions

Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)

Group III: 1/Safety Lead-in Combination Therapy (closed December 2018) Experimental Treatment 8 Interventions

Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01322490

Study Details | NCT01322490 | A Randomized, Double- ... The purpose of this study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494360/

Phase III Trial of PROSTVAC in Asymptomatic or Minimally ... PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.5006

Results of PROSPECT: A randomized phase 3 trial ... Secondary endpoints: Alive without event at 6 months (AWE-6) and Safety. Results: Between Dec 2011 and Jan 2015, 1297 pts were randomized in 15 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7985967/

Phase I Trial of M7824 (MSB0011359C), a Bifunctional ... There were signs of efficacy across all dose levels, including one ongoing confirmed complete response (cervical cancer), two durable confirmed partial ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03315871

Combination Immunotherapy in Biochemically Recurrent ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02840994

NCT02840994 | A Trial of CV301 in Combination With Anti- ... The objective of the proposed clinical trial is to investigate the safety and tolerability of CV301 in combination with Anti-PD1-Therapy in subjects with non- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10992231/

Phase II trial of CV301 vaccine combined with ... CV301 has demonstrated an acceptable safety profile as monotherapy or in combination with PD1 inhibitors in phase I clinical trials [5], 6, 7].

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.511

Phase 2 trial of CV301 vaccine plus atezolizumab (Atezo) ... CV301 + atezo exhibited an acceptable safety profile but did not demonstrate sufficient efficacy in pts with aUC as 1st-line therapy in cisplatin-ineligible ...

9. nature.com nature.com/articles/s41391-021-00402-8

Safety and preliminary immunogenicity of JNJ-64041809, a ... JNJ-809 has manageable safety consistent with other LADD Lm-based therapies. Limited antigen-specific immune responses were observed, which did not translate ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa1014618

Abiraterone and Increased Survival in Metastatic Prostate ... We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant ...