Nivolumab + Ipilimumab for Prostate Cancer

(CheckMate 650 Trial)

No longer recruiting at 130 trial locations

Overseen By First line of the email MUST contain NCT# and Site #.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must be taking: GnRH analogues

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Liver metastases, Brain 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: 8

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments—nivolumab (an immunotherapy drug) followed by ipilimumab (another immunotherapy drug)—to evaluate their effectiveness for a specific type of prostate cancer that has spread and does not respond to standard hormone treatments. Researchers aim to determine if these drugs can effectively slow or stop the cancer and assess their safety and tolerability. Individuals with metastatic prostate cancer (cancer that has spread beyond the prostate) who are still undergoing hormone therapy might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue ongoing androgen deprivation therapy (ADT).

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

Research has shown that the combination of nivolumab and ipilimumab has been tested for safety in patients with advanced prostate cancer that no longer responds to hormone therapy. The safety profile of these drugs together aligns with previous studies, indicating they generally act as expected when combined. Some patients have experienced serious side effects, which can be severe.

However, this combination has helped some patients, particularly those with certain genetic traits. Prospective participants should discuss the potential risks and benefits with their doctor to determine if joining a trial is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard prostate cancer treatments, which often involve hormone therapy or chemotherapy alone, the combination of Nivolumab and Ipilimumab introduces a novel approach by engaging the immune system to fight cancer. These drugs are immune checkpoint inhibitors that work by blocking proteins that prevent immune cells from attacking cancer cells, potentially leading to a more robust, targeted response against tumors. This combination therapy could offer a new avenue for patients who have not responded well to traditional treatments, providing hope for more effective management of advanced prostate cancer. Researchers are particularly excited about the potential for these drugs to enhance the body’s own defenses to combat cancer more effectively than current options.

What evidence suggests that this trial's treatments could be effective for metastatic castration resistant prostate cancer?

In this trial, participants will receive different combinations of treatments. One combination under study is nivolumab and ipilimumab, which showed promising results in previous studies for patients with advanced prostate cancer unresponsive to standard hormone treatments. This combination is among the first to demonstrate effectiveness in this challenging condition. Research suggests these drugs help the immune system better identify and attack cancer cells. Other studies have also shown improved outcomes when these drugs are used together, indicating potential effectiveness for treating this type of prostate cancer. While many questions remain, early results encourage those considering this treatment option. ^{1 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that has spread and is resistant to hormone therapy can join. They should be relatively healthy (ECOG 0-1) and on hormone-blocking treatment with low testosterone levels. Men who've had certain recent treatments, active autoimmune diseases, liver metastases, brain tumors, or previous immunotherapy are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

I was previously in Arm D3 or D4 of the trial, have prostate cancer confirmed by tests, and it's stage IV.

My scans show cancer has spread to my bones or soft tissues.

Exclusion Criteria

I have been treated with specific immune system targeting drugs before.

I have received cancer treatment after my last dose of the study medication.

I have an autoimmune disease or a current infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab followed by ipilimumab or cabazitaxel for metastatic castration-resistant prostate cancer

6 months

Tumor assessments every 8 weeks for 6 months, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for radiographic progression-free survival and overall survival

Up to 61 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Ipilimumab
• Nivolumab
• Prednisone

Trial Overview The trial tests the effectiveness of Nivolumab followed by Ipilimumab versus each drug alone or Cabazitaxel in treating metastatic castration-resistant prostate cancer. It aims to see which combination is safer and more tolerable for patients.

How Is the Trial Designed?

Group I: Cohort D (Arm D4) Experimental Treatment 2 Interventions

Group II: Cohort D (Arm D3) Experimental Treatment 1 Intervention

Group III: Cohort D (Arm D2) Experimental Treatment 2 Interventions

Group IV: Cohort D (Arm D1) Experimental Treatment 2 Interventions

Group V: Cohort C (Arm C) Experimental Treatment 2 Interventions

Group VI: Cohort B (Arm B) Experimental Treatment 2 Interventions

Group VII: Cohort A (Arm A) Experimental Treatment 2 Interventions

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. news.bms.com news.bms.com/news/corporate-financial/2019/Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Shows-Response-in-Pre-Treated-Patients-with-Metastatic-Castration-Resistant-Prostate-Cancer/default.aspx

Opdivo (nivolumab) Plus Yervoy (ipilimumab) Shows ... First I-O/I-O combination regimen to demonstrate response rates in this hard-to-treat patient population.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02985957

NCT02985957 | A Study of Nivolumab Plus Ipilimumab, ... The purpose of this study is to evaluate the effectiveness, safety and tolerability of nivolumab followed by ipilimumab, in subjects with metastatic castration ...

3. cancernetwork.com cancernetwork.com/view/addition-of-sbrt-to-nivolumab-ipilimumab-does-not-improve-response-in-mcrpc

Addition of SBRT to Nivolumab/Ipilimumab Does Not ... The median PSA progression-free survival (PFS) for arm A was 2.6 months (95% CI, 1.9-3.8), and for arm B it was 2.5 months (95% CI, 1.9-3.0).

4. targetedonc.com targetedonc.com/view/nivolumab-ipilimumab-chemotherapy-combo-achieves-long-term-os-in-nsclc

Nivolumab/Ipilimumab/Chemotherapy Combo Achieves ... At 5 years, 72% vs 35% of patients, respectively, were treatment-free. Investigators also reported a 5-year progression-free survival (PFS) rate ...

5. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Efficacy ... In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0923753424039991

Ipilimumab with nivolumab in molecularly selected patients ... Ipilimumab and nivolumab induced a 6-month DCR of 38% in patients with molecularly selected mCRPC. •. Durable benefit was particularly high in patients with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39293514/

primary analysis of the phase II INSPIRE trial This trial of dual ICIs in molecularly selected mCRPC met its primary endpoint, showing DCR > 6 in 38% of patients.

8. asco.org asco.org/abstracts-presentations/ABSTRACT395778

Additional results from the randomized phase 2 CheckMate ... Outcomes included safety, objective response rate (ORR), prostate-specific antigen response rate (PSA-RR; confirmed PSA decline ≥ 50% from baseline) ...

9. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT138/742480/Abstract-CT138-Evaluating-nivolumab-nivo-plus

Evaluating nivolumab (nivo) plus ipilimumab (ipi) in patients ... Conclusions: Across both arms, ipi/nivo induced clinical responses and increased %CD8 in a subset of “cold” mCRPC tumors with low CD8 cells.