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
Prostate cancer
The study will be conducted in 2 Parts: Part 1: Dose Confirmation Participants will receive JNJ-78278343 (Pasritamig) in combination with JNJ-95298177 (ARX517) in a dose de-escalation schedule in accordance with the Bayesian Optimal Interval Design (BOIN) design to determine the recommended phase 2 combination dose (RP2CD) regimen. Part 2: Dose Expansion Participants will receive JNJ-78278343 in combination with JNJ-95298177 at the RP2CD as determined in Part 1 of the study to confirm the safety and anti-tumor activity. Both drugs will be administered intravenously. Follow up for around 2 years 2 months.
1. 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 NEmarker positivity) are allowed 2. Must have metastatic castration-resistant prostate cancer (mCRPC) 3. PSA must measure at least 2 nanograms per milliliters (ng/mL) at screening 4. Measurable or evaluable disease 5. 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 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Current key exclusion criteria as of 16/04/2026: 1. 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) 2. Known allergies, hypersensitivity, or intolerance to any of the components (e.g., excipients) of JNJ-78278343 or JNJ-95298177 3. 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 4. 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: 4.1. 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 4.2. Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment 4.3. Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment 4.4. Any prior treatment with kallikrein-related peptidase 2 (KLK2)-targeted therapy 4.5. Any prior prostate-specific membrane antigen (PSMA)-targeting therapy (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 4.6. Any prior antibody drug conjugates (ADCs) with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins) 5. 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 info