Checkpoint Inhibitor

Pembrolizumab for Prostate Cancer (CHOMP Trial)

Philadelphia, PA

Phase 2

Recruiting

Led By Matthew B. Rettig, MD

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

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

Must have

Adequate organ function: Hemoglobin (hgb) > 9.0 g/dL, Absolute neutrophil count (ANC) > 1500/ uL, Platelets > 100,000/ uL, Total bilirubin 1.5 x ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 x ULN ALT and AST 2.5 x ULN ( 5 x ULN for participants with liver metastases) (Child-Pugh class A and B allowed; Child-Pugh class C is excluded). Creatinine < (2.0 mg/dL) during screening evaluation (>2.0 is allowed if EGFR >30 mL/min/1.73 m2). Subject must agree to use contraception during the treatment period plus an additional 120 days after the last dose of study treatment and must refrain from donating sperm during this period.

Progressive castration resistant prostate cancer as defined by serum testosterone < 50 ng/mL and one of the following: PSA progression confirmed per Prostate Cancer Clinical Trials Working Group (PCWG3), Radiographic progression of soft tissues according to Response Evaluation Criteria in Solid Tumors, version 1.1 (iRECIST 1.1) modified based on PCWG3, or radiographic progression of bone according to PCWG3. Prior use of a novel AR signaling inhibitor for 4 weeks, including abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and/or darolutamide. NOTE: These AR signaling inhibitors may have been used for mCSPC, M0CRPC, and/or mCRPC.

Must not have

Brain metastases.

Vaccinated with a live vaccine within 30 days of enrollment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up first day of pembrolizumab administration to 6 months after

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing the efficacy of pembrolizumab, a checkpoint inhibitor, in Veterans with metastatic castration-resistant prostate cancer. The study will also compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab.

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Who is the study for?

Men with advanced prostate cancer that's resistant to hormone therapy and has specific genetic changes (mismatch repair deficiency or CDK12 inactivation) can join. They must be adults, have a good performance status, agree to use contraception, and not have brain metastases or active infections. Prior treatments for cancer should be completed before joining.Check my eligibility

What is being tested?

The trial is testing pembrolizumab, an immune checkpoint inhibitor, on its effectiveness against certain types of advanced prostate cancer. It will also compare tumor samples before and after treatment to understand resistance or sensitivity to the drug.See study design

What are the potential side effects?

Pembrolizumab may cause immune-related side effects like inflammation in various organs including lungs (pneumonitis), liver issues, skin reactions, hormonal gland problems (like thyroid dysfunction), fatigue, infusion reactions and possibly other autoimmune-like conditions.

Eligibility Criteria

Inclusion Criteria

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

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My prostate cancer is worsening despite low testosterone, and I've used specific prostate cancer medications for at least 4 weeks.

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My prostate cancer is worsening despite low testosterone levels.

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My liver function tests are within the required range.

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I can carry out all my daily activities without help.

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I am 18 years old or older.

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My prostate cancer is diagnosed as adenocarcinoma or small cell.

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I have been treated with specific prostate cancer medications for at least 4 weeks.

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My cancer has grown or spread according to recent scans.

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My cancer has specific genetic changes (dMMR or CDK12-/-).

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My genetic test shows changes in the CDK12 gene.

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Exclusion Criteria

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

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My cancer has spread to my brain.

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

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I am highly allergic to pembrolizumab or its ingredients.

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I have an active tuberculosis infection.

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I have been treated with specific immune therapy drugs before.

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I have had or currently have lung inflammation treated with steroids.

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I am currently being treated for an infection with antibiotics.

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I have an autoimmune disease or have taken immunosuppressive drugs in the last 2 years.

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I haven't taken high doses of steroids or similar medications in the last 2 weeks.

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Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ first day of pembrolizumab administration to 6 months after

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~first day of pembrolizumab administration to 6 months after

This trial's timeline: 3 weeks for screening, Varies for treatment, and first day of pembrolizumab administration to 6 months after for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate

PSA Decline

Secondary study objectives

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Maximum PSA Response

Overall Survival

+1 more

Other study objectives

Identification of Molecular Correlates and Biomarkers of Resistance and Sensitivity to Pembrolizumab

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Vomiting

33%

Dysgeusia

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Alanine aminotransferase increased

20%

Hypoacusis

20%

Hyponatraemia

19%

Tinnitus

19%

Asthenia

19%

Oral candidiasis

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hypoalbuminaemia

10%

Hyperthyroidism

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Peripheral sensory neuropathy

Neck pain

Hyperglycaemia

Gastrooesophageal reflux disease

Hyperuricaemia

Hypophosphataemia

Dizziness

Hiccups

Hyperkalaemia

Ear pain

Oral pain

Localised oedema

Urinary tract infection

Erythema

Anxiety

Abdominal pain upper

Dyspepsia

Saliva altered

Arthralgia

Febrile neutropenia

Back pain

Dyspnoea

Hypertension

Oedema peripheral

Nasopharyngitis

Alopecia

Dry skin

Laryngeal oedema

Sepsis

Pneumonitis

Trismus

Pneumonia aspiration

Cellulitis

Malnutrition

Pharyngeal haemorrhage

Septic shock

Abscess neck

Bronchitis

Stoma site infection

Colitis

Mouth haemorrhage

Oesophagitis

General physical health deterioration

Hepatitis

Immune-mediated hepatitis

Hypersensitivity

Clostridium difficile colitis

Device related infection

Systemic infection

Vascular device infection

Wound infection

Hypercalcaemia

Hypophagia

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Pulmonary embolism

Respiratory failure

Tumour haemorrhage

Death

Acute myocardial infarction

Cardiac arrest

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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 ArmExperimental Treatment1 Intervention

This is a single-arm, open-label study of the checkpoint inhibitor, pembrolizumab, in Veterans with mCRPC who have progressed on at least 1 prior novel androgen receptor (AR) signaling inhibitor, inclusive of abiraterone acetate, enzalutamide, apalutamide, and darolutamide. In addition to progressive mCRPC, a patient must have a somatic tumor mutation characterized by dMMR or CDK12-/- detected by next generation sequencing (NGS). Patients enrolled in this study will be treated with pembrolizumab at the FDA approved dosage of 200 mg intravenously every 3 weeks (21 days) until disease progression or unacceptable toxicity. During study, patients will maintain a castrate level of testosterone, = 50 ng/dL by ongoing treatment with a GnRH analogue or prior bilateral orchiectomy. Prior to initiating treatment with pembrolizumab, patients will undergo a baseline biopsy of a metastatic lesion. An additional biopsy of a metastatic lesion at the time of progression will be encouraged as well.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

FDA approved

0 / 20Eligibility criteria met