Combination treatment with JNJ-78278343 and JNJ-95298177 for prostate cancer

A Phase 1b Study of JNJ-78278343, a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With JNJ-95298177, an Antibody Drug Conjugate Targeting Prostate Specific Membrane Antigen, for Prostate Cancer

This trial tests whether giving two experimental drugs together, JNJ-78278343 and JNJ-95298177, is safe and tolerable for men with metastatic castration-resistant prostate cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Janssen Research & Development, LLC (Industry-sponsored)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor
• Locations: 6 sites (Sarasota, Florida and 5 other locations)
• Trial ID: NCT07082920 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label trial has two parts: Part 1 will confirm dose levels to identify a recommended phase 2 combination dose (RP2CD), and Part 2 will expand at that dose to further characterize safety and tolerability in participants with metastatic castration-resistant prostate cancer (mCRPC). Eligible participants have histologically confirmed prostate adenocarcinoma (with certain neuroendocrine-feature exceptions), measurable or evaluable disease, PSA ≥2 ng/mL, and ECOG 0–1 while on continuous androgen-deprivation therapy. Participants receive combination dosing of JNJ-78278343 and JNJ-95298177 with safety monitoring and disease assessments per protocol. The primary goal is to define a tolerable combination dose and characterize adverse events and tolerability in this patient population.

Who should consider this trial

Good fit: Men with histologically confirmed prostate adenocarcinoma who have metastatic castration-resistant disease, PSA ≥2 ng/mL, measurable or evaluable disease, are on continuous androgen-deprivation therapy, and have ECOG performance status 0 or 1 are ideal candidates.

Not a fit: Patients with primary small cell or large cell neuroendocrine prostate cancers, those not meeting the PSA or metastatic criteria, or those with poor performance status are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could offer a new tolerable treatment option that may help control disease in men with mCRPC.

How similar studies have performed: These specific agents are experimental and while some early-phase combination approaches in prostate cancer have shown mixed signals, direct clinical evidence for this exact combination is limited.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate. Primary small cell carcinoma, carcinoid tumor, neuroendocrine (NE) carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (for example \[e.g.\], immunohistochemistry \[IHC\] with both androgen receptor \[AR\]- and NE-marker positivity) are allowed
* Must have metastatic castration-resistant prostate cancer (mCRPC)
* PSA must measure at least 2 nanograms per milliliters (ng/mL) at screening
* Measurable or evaluable disease
* Prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analog (agonist or antagonist) prior to the first dose of study drug and must continue this therapy throughout the treatment phase
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion criteria:

* Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to (\<=) 1 or baseline levels (except for alopecia and vitiligo)
* Known allergies, hypersensitivity, or intolerance to any of the components (e.g., excipients) of JNJ-78278343 or JNJ-95298177
* Participants with leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic greater than (\>) 2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment
* Treatment with any anti-cancer or investigational agents within 14 days prior to the first dose of study treatment; specific requirements for certain anti-cancer therapies are as follows:

  1. Any T-cell redirecting treatment (e.g., CD3-directed bispecific or Chimeric Antigen Receptor T-cell \[CAR-T\] therapy) within 90 days prior to the first dose of study treatment
  2. Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment
  3. Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment
  4. Any prior treatment with kallikrein-related peptidase 2 (KLK2)-targeted therapy
  5. Any prior prostate-specific membrane antigen (PSMA)-targeting therapy (that is \[i.e.\], participants who received PSMA-targeting radioconjugates are excluded) \[Parts 2A and 2B only\]. Prior PSMA RLT is allowed in Part 1 and required for Part 2C and Part 2D but last dose must be \>3 months prior to the first dose of study treatment
  6. Any prior antibody drug conjugates (ADCs) with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins)
* Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments

Where this trial is running

Sarasota, Florida and 5 other locations

• Florida Cancer Specialists — Sarasota, Florida, United States (Recruiting)
• Columbia University Medical Center — New York, New York, United States (Recruiting)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)
• The Christie Nhs Foundation Trust — Manchester, United Kingdom (Recruiting)
• Royal Marsden Hospital (Sutton) — Sutton, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Study Contact

Conditions Prostatic Neoplasms