Vudalimab + Chemotherapy/Targeted Therapy for Prostate Cancer

Recruiting at 27 trial locations

Overseen By Amber Sarot

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Xencor, Inc.

Must be taking: Androgen suppression

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: CNS metastases, Autoimmune disease, 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: Unknown

Duration: 12 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 2 study will investigate the safety and clinical activity of vudalimab (XmAb20717) alone or in combination with standard of care anticancer therapies in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer therapies other than androgen deprivation therapy at least 2 weeks before starting the study drug. If you are currently taking prednisone for prostate cancer, you can continue it during the study.

What data supports the effectiveness of the drug Vudalimab + Chemotherapy/Targeted Therapy for Prostate Cancer?

The research indicates that while immune checkpoint inhibitors like those in Vudalimab have shown limited benefits in prostate cancer, certain subgroups of patients with specific genetic markers may respond better. For example, patients with DNA mismatch repair deficiency (dMMR) or high PD-L1 expression might experience improved outcomes with these treatments. ^{1 2 3 4 5}

What safety data exists for Vudalimab and related therapies in humans?

The safety data for therapies similar to Vudalimab, such as anti-PD-1 and anti-CTLA-4 antibodies, indicate that they can cause immune-related side effects, which may include muscle inflammation (myositis) and thyroid issues (hypothyroidism). These side effects can be serious if not managed properly. ^{2 6 7 8 9}

What makes the drug Vudalimab unique for prostate cancer treatment?

Vudalimab is a novel bispecific antibody that targets both PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system. This dual-targeting approach is unique compared to traditional treatments that typically focus on a single target, potentially enhancing the immune response against prostate cancer. ^{1 2 3 10 11}

Research Team

Jolene Shorr

Principal Investigator

Xencor, Inc.

Eligibility Criteria

This trial is for adults with metastatic castration-resistant prostate cancer who've had at least two prior anticancer treatments. Participants must have a confirmed diagnosis, documented disease progression, and be on or willing to continue androgen suppression if not surgically castrated. They should have specific genetic profiles based on the cohort they fit into and must not be receiving other anticancer therapies.

Inclusion Criteria

Able to provide written informed consent

I am on hormone therapy to lower testosterone and willing to continue it.

I am willing and able to follow the study's schedule.

Exclusion Criteria

I have not received a live-virus vaccine in the last 30 days.

I have recovered from previous cancer treatment side effects to a mild level.

I do not have HIV or hepatitis B/C, or it is under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XmAb20717 alone or in combination with chemotherapy or targeted therapies

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Cabazitaxel
• Carboplatin
• Olaparib
• XmAb20717

Trial Overview The study tests vudalimab (XmAb20717) alone or combined with chemotherapy or targeted therapy in patients with advanced prostate cancer. It aims to assess safety and effectiveness after previous treatments failed. The combinations include vudalimab with olaparib, cabazitaxel or docetaxel, carboplatin plus one of the taxanes, or as monotherapy.

Participant Groups

Group I: Cohort E - No Targetable Mutations Experimental Treatment 2 Interventions

XmAb20717 + carboplatin + cabazitaxel

Group II: Cohort D - MSI-H, MMRD or TMB-H Experimental Treatment 1 Intervention

Group III: Cohort C - HRD/CDK12 PARP Naïve Experimental Treatment 1 Intervention

XmAb20717 + olaparib

Group IV: Cohort B - HRD/CDK12 PARP - Progressors Experimental Treatment 1 Intervention

XmAb20717 + carboplatin + cabazitaxel

Group V: Cohort A - AVPCa Experimental Treatment 1 Intervention

XmAb20717 + carboplatin + cabazitaxel

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

Findings from Research

The novel bispecific antibody CCW702 effectively targets metastatic castration-resistant prostate cancer (mCRPC) by combining T cell recruitment with specificity for prostate-specific membrane antigen, showing potent in vitro cytotoxicity and improved stability compared to previous formats.

In animal studies, CCW702 demonstrated significant tumor elimination with just three doses and was well tolerated in cynomolgus monkeys, supporting its potential for a weekly dosing regimen in upcoming human trials for patients with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand. Lee, SC., Ma, JSY., Kim, MS., et al.[2022]

A small subset of metastatic castration-resistant prostate cancers (mCRPC) with DNA mismatch repair deficiency (dMMR) can respond to checkpoint inhibitors like pembrolizumab, but responses may be limited over time.

In a unique case, a patient who initially progressed on pembrolizumab after a response was successfully re-sensitized to the treatment after receiving a bispecific T-cell engager antibody (JNJ-081), leading to a significant reduction in prostate-specific antigen levels for over 11 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-sensitization to pembrolizumab following PSMA-CD3 T-cell redirection therapy with JNJ-081 in a patient with mismatch repair-deficient metastatic castration-resistant prostate cancer: a case report. Reed-Perino, DE., Lai, M., Yu, EY., et al.[2023]

Recent advancements in prostate cancer treatment include new drugs like abiraterone acetate and enzalutamide, which effectively target androgen receptor signaling and have shown significant benefits when combined with androgen deprivation therapy (ADT) for advanced stages of the disease.

Ongoing clinical trials are exploring various innovative therapies, including second-generation AR antagonists and targeted treatments based on molecular profiling, which aim to personalize and improve treatment outcomes for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in Prostate Cancer Treatment and Drug Discovery. Nevedomskaya, E., Baumgart, SJ., Haendler, B.[2022]

In a study of 10 patients with metastatic prostate cancer treated with ipilimumab, none achieved the primary endpoint of undetectable PSA levels, leading to the study's early termination; however, 30% showed a significant reduction in PSA levels, indicating some potential efficacy.

Analysis of blood samples revealed that patients who responded to treatment had an increase in specific T-cell subsets, suggesting that ipilimumab may induce a Th1 immune response, which could be important for identifying patients who might benefit from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy. Graff, JN., Stein, MN., Surana, R., et al.[2020]

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

In a pilot study involving 14 patients with hormone-refractory prostate cancer, a single dose of 3 mg/kg of the anti-CTLA-4 antibody Ipilimumab was found to be safe, with only one patient experiencing significant clinical autoimmunity (grade 3 rash).

Two patients showed a notable decline in prostate-specific antigen (PSA) levels of 50% or more, suggesting that Ipilimumab may have potential for modulating PSA levels and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Small, EJ., Tchekmedyian, NS., Rini, BI., et al.[2017]

Monoclonal antibodies targeting CTLA-4 and PD-1 have been approved for treating metastatic melanoma, advanced non-small-cell lung cancer, and metastatic renal cancer, demonstrating significant efficacy in these conditions.

These immune checkpoint inhibitors can cause serious immune-related adverse events, which require careful management and awareness from oncologists to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of immune checkpoint inhibitors used to treat melanoma and other cancer]. Jacquin-Porretaz, C., Nardin, C., Puzenat, E., et al.[2017]

In a study of 1346 prostate cancer patients, only 3.1% were found to have microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, indicating that this molecular phenotype is rare but significant for treatment options.

Among 11 patients with MSI-H/dMMR castration-resistant prostate cancer who received anti-PD-1/PD-L1 therapy, 54.5% experienced a significant decline in prostate-specific antigen levels, suggesting that this therapy can be effective for some patients with this specific tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. Abida, W., Cheng, ML., Armenia, J., et al.[2022]

In a phase II trial involving men with metastatic castration-resistant prostate cancer (mCRPC) who were progressing on enzalutamide, the anti-PD-1 antibody pembrolizumab showed unexpected antitumor activity, with three out of ten patients achieving significant reductions in prostate-specific antigen (PSA) levels.

The presence of immune cell infiltrates and PD-L1 expression in tumor biopsies from responders suggests that certain biological markers may predict the effectiveness of PD-1 inhibitors in prostate cancer, warranting further investigation into this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Graff, JN., Alumkal, JJ., Drake, CG., et al.[2022]

Pasotuxizumab, a bispecific T-cell engager, was found to be safe for patients with advanced castration-resistant prostate cancer, with a maximum tolerated dose of 172.0 μg/d established for subcutaneous administration.

The treatment showed promising efficacy, with 9 patients achieving over 50% decline in PSA levels from subcutaneous administration and 3 from continuous intravenous infusion, indicating potential for long-term responses in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. Hummel, HD., Kufer, P., Grüllich, C., et al.[2023]

In a Phase Ib/II trial involving 86 patients with metastatic castrate-resistant prostate cancer (mCRPC), the combination of xentuzumab and enzalutamide was well tolerated, with no dose-limiting toxicities reported during the Phase Ib escalation.

While the combination showed a median progression-free survival (PFS) of 7.4 months compared to 6.2 months for enzalutamide alone, it ultimately lacked significant antitumor activity in the overall patient population, suggesting that further selection criteria may be needed for efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. Macaulay, VM., Lord, S., Hussain, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Re-sensitization to pembrolizumab following PSMA-CD3 T-cell redirection therapy with JNJ-081 in a patient with mismatch repair-deficient metastatic castration-resistant prostate cancer: a case report. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances in Prostate Cancer Treatment and Drug Discovery. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. [2017]

7. France pubmed.ncbi.nlm.nih.gov

[Adverse effects of immune checkpoint inhibitors used to treat melanoma and other cancer]. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. [2023]

11. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. [2023]