What side effects are associated with this type of intervention?

Common side effects of androgen receptor (AR) blockers like apalutamide include fatigue, hypertension, rash, diarrhea, and falls. Immune checkpoint inhibitors, such as cetrelimab, can cause immune-related adverse events including colitis, hepatitis, endocrinopathies (like thyroid dysfunction), and pneumonitis. Combining these treatments may lead to a cumulative side effect profile, necessitating careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that involve androgen receptor (AR) blockade and immune checkpoint inhibition. Apalutamide, an AR blocker, was approved for metastatic castration-sensitive prostate cancer (CSPC) and non-metastatic castration-resistant prostate cancer (CRPC). Enzalutamide, another AR blocker, has similar approvals for both metastatic and non-metastatic CRPC. Immune checkpoint inhibitors like Pembrolizumab have been approved for metastatic CRPC with specific genetic markers such as dMMR or high TMB. These treatments aim to inhibit androgen receptor signaling and enhance immune response against cancer cells, respectively.

What other types of research exist?

Promising alternatives to Apalutamide + Cetrelimab for prostate cancer treatment include: 1) Darolutamide combined with docetaxel and ADT, which has shown a significant survival benefit in metastatic castration-sensitive prostate cancer (CSPC). 2) Abiraterone combined with PARP inhibitors like niraparib or olaparib, which have demonstrated improved progression-free survival in patients with homologous recombination repair (HRR) deficiencies. 3) Bipolar androgen therapy (BAT) followed by retreatment with abiraterone or enzalutamide, which has shown potential in restoring sensitivity to these agents in castration-resistant prostate cancer (CRPC).

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Hormone Therapy

Apalutamide + Cetrelimab for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen receptor (AR) pathway and the immune system. AR blockade, as seen with drugs like Apalutamide, inhibits the binding of androgens to their receptors, preventing the activation of AR-driven transcriptional programs that promote cancer cell growth. This is crucial because prostate cancer cells typically rely on androgens for proliferation. Immune checkpoint inhibitors, such as Cetrelimab, work by blocking proteins like PD-1 on immune cells, which cancer cells exploit to evade immune detection. By inhibiting these checkpoints, the immune system can better recognize and attack cancer cells. Combining AR blockade with immune checkpoint inhibition may provide a synergistic effect, potentially leading to more durable and effective responses in prostate cancer patients.

Phase 2

Waitlist Available

Led By Rahul Aggarwal, MD

Research Sponsored by Rahul Aggarwal

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must be evaluable for the primary endpoint of composite response and must have either serum Prostate-specific antigen (PSA) > 2 ng/mL during screening and/or measurable disease by RECIST 1.1 criteria.

Prior progression on at least one androgen signaling inhibitor (e.g. abiraterone acetate, apalutamide, enzalutamide, darolutamide).

Must not have

Concurrent second malignancy requiring active treatment at study entry that could affect safety or efficacy endpoints.

Diagnosis of immunodeficiency or receiving systemic steroid therapy at a prednisone equivalent dose of > 10 mg daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, apalutamide and cetrelimab, in patients with a hard-to-treat form of prostate cancer. Apalutamide blocks male hormones that help cancer grow, and cetrelimab boosts the immune system to fight the cancer. The goal is to see if this combination can effectively treat patients who haven't responded to other treatments.

Who is the study for?

This trial is for men aged 18+ with prostate cancer that has become resistant to hormone therapy and shows small cell neuroendocrine features. They must have had no more than one prior chemo in the metastatic setting, be able to perform daily activities (ECOG <=1), and agree to use contraception. Excluded are those with certain immune conditions, recent vaccines or other treatments, infections needing IV antibiotics, gastrointestinal absorption issues, or a history of seizures.

What is being tested?

The study tests if adding apalutamide (a drug blocking male hormones) to cetrelimab (an immunotherapy drug) can help patients whose prostate cancer has changed into a form not driven by male hormones. Participants will receive both drugs and their response will be monitored through clinical assessments.

What are the potential side effects?

Possible side effects include fatigue, rash, diarrhea, joint pain from apalutamide; cetrelimab may cause immune-related reactions like inflammation in organs such as lungs or intestines, skin rashes or liver problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My PSA level is over 2 ng/mL or my cancer can be measured by scans.

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My cancer progressed despite treatment with drugs like abiraterone.

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I am 18 years old or older.

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My testosterone levels are very low, and I am on or will stay on hormone therapy if I haven't had surgery to remove my testicles.

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I am fully active or can carry out light work.

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My prostate cancer has worsened recently.

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My prostate cancer has changed into a more aggressive form with specific genetic changes.

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My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have another cancer that needs treatment during this study.

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I am not on high-dose steroids or other drugs that weaken my immune system.

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I have had pneumonitis treated with steroids or currently have it.

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I have not needed IV antibiotics for an infection in the last week.

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I have a digestive condition that affects how my body absorbs nutrients.

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I have previously received treatments targeting my immune system.

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My prostate cancer is a specific type called 'small cell carcinoma' from the start.

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I have a heart condition.

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I have an active hepatitis B or C infection with a detectable viral load.

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I have had seizures or a condition that could lead to seizures.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Composite Response Rate

Secondary study objectives

Median Duration of Response

Median Overall Survival

Median PSA progression-free survival (PFS)

+5 more

Side effects data

From 2021 Phase 2 trial • 86 Patients • NCT03279250

74%

Hot flashes

71%

Fatigue

44%

Anemia

38%

Hyperglycemia

26%

AST increase

26%

Hypertension

26%

Lipase increase

24%

ALT increase

24%

Dry skin

21%

Rash

18%

ACTH increase

18%

Cholesterol high

15%

Dizziness

15%

Amylase increase

12%

Memory impairment

12%

White blood cell decrease

12%

Constipation

12%

Lymphocyte count decrease

Myalgia

Paresthesia

Weight loss

Arthralgia

Hypothyrodism

LDH increase

Erectile dysfunction

Headache

Personality change

Dysgeusia

Dyspnea

HbA1c increased

Hypertriglyceridemia

Insomnia

Irritability

Anorexia

Atrial fibrillation

Anxiety

Bruising

Hypercalcemia

Dehydration

TSH increased

100%

80%

60%

40%

20%

Study treatment Arm

Arm B (LHRHa, Apalutamide, Abiraterone Acetate)

Arm A (LHRHa, Apalutamide)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single Arm: Apalutamide + CetrelimabExperimental Treatment2 Interventions

Participants will be given Apalutamide tablets combined with infusions of Cetrelimab in 28-day cycles, for up maximum of two years.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Apalutamide

2015

Completed Phase 2

~5750

Cetrelimab

2022

Completed Phase 1

~20

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor (AR) pathway and the immune system. AR blockade, as seen with drugs like Apalutamide, inhibits the binding of androgens to their receptors, preventing the activation of AR-driven transcriptional programs that promote cancer cell growth. This is crucial because prostate cancer cells typically rely on androgens for proliferation. Immune checkpoint inhibitors, such as Cetrelimab, work by blocking proteins like PD-1 on immune cells, which cancer cells exploit to evade immune detection. By inhibiting these checkpoints, the immune system can better recognize and attack cancer cells. Combining AR blockade with immune checkpoint inhibition may provide a synergistic effect, potentially leading to more durable and effective responses in prostate cancer patients.