Investigational Drug
JNJ-78278343
TrialFetch AI Analysis
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Overview
Pasritamig (JNJ-78278343) is an investigational T‑cell–engaging bispecific antibody being developed by Johnson & Johnson for metastatic castration‑resistant prostate cancer (mCRPC). First‑in‑human, phase 1 results were presented at ASCO 2025 and published in the Journal of Clinical Oncology (JCO) on June 1, 2025. A global phase 3 trial in late‑line mCRPC is under way. (pubmed.ncbi.nlm.nih.gov)
Mechanism of action
- Target: human kallikrein 2 (KLK2), a prostate‑specific antigen with minimal expression outside the prostate. Pasritamig binds KLK2 on tumor cells and CD3 on T cells to redirect T‑cell cytotoxicity toward prostate cancer cells. (jnj.com)
Efficacy
Phase 1 (NCT04898634; JCO 2025): - Population: 174 patients with mCRPC; median 4 prior systemic therapies. The recommended phase 2 dose (RP2D) was IV 3.5 mg (day 1), 18 mg (day 8), 300 mg (day 15), then 300 mg every 6 weeks. (pubmed.ncbi.nlm.nih.gov) - RP2D efficacy cohort (n = 33): - PSA50 response (≥50% decline in PSA): 42.4% at any time. (pubmed.ncbi.nlm.nih.gov) - Median radiographic PFS: 7.85 months (95% CI, 2.89 to not estimable). (pubmed.ncbi.nlm.nih.gov)
Note: The JCO abstract reports PSA and rPFS endpoints; objective response data in measurable disease were limited in the abstract. (pubmed.ncbi.nlm.nih.gov)
Safety
Phase 1 (all treated n = 174): - Treatment‑related adverse events (TRAEs): 82.8% any grade; grade ≥3 in 9.8%. (pubmed.ncbi.nlm.nih.gov) - RP2D safety cohort (n = 45): most common TRAEs were infusion‑related reactions (24.4%), fatigue (15.6%), and cytokine release syndrome (CRS) 8.9% (all grade 1). The sponsor’s release additionally notes no ICANS, no TRAE‑related discontinuations or dose reductions, and infrequent grade 3 lab abnormalities (transient AST/ALT increase and neutropenia, each 4.4%). (pubmed.ncbi.nlm.nih.gov) - Outpatient feasibility: low‑grade CRS and overall tolerability supported outpatient administration on a once‑every‑6‑weeks schedule at RP2D. (pubmed.ncbi.nlm.nih.gov)
Ongoing/Planned trials
- Phase 1 (dose escalation/expansion): NCT04898634; active, evaluating safety, RP2D, and preliminary antitumor activity. (clinicaltrials.gov)
- Phase 3 (KLK2‑comPAS): NCT07164443, randomized, double‑blind, placebo‑controlled study of pasritamig + best supportive care versus placebo + best supportive care in late‑line mCRPC; primary endpoint overall survival; recruiting across multiple countries as of September 2025. (clinicaltrials.jnj.com)
Further reading
- Journal article: Pasritamig, a First‑in‑Class, Bispecific T‑Cell Engager Targeting Human Kallikrein 2, in mCRPC (JCO 2025; PubMed record). (pubmed.ncbi.nlm.nih.gov)
- Phase 1 trial record: NCT04898634 (ClinicalTrials.gov). (clinicaltrials.gov)
- Sponsor press release summarizing ASCO 2025 data and RP2D regimen. (jnj.com)
- Phase 3 trial overview (JNJ trial page) and independent listing (ANZCTR/Dana‑Farber). (clinicaltrials.jnj.com)
Notes: Pasritamig is investigational and not approved; data are early and primarily from a phase 1 study. Phase 3 outcomes will clarify survival benefit and risk–benefit in late‑line mCRPC. (pubmed.ncbi.nlm.nih.gov)
Last updated: Oct 2025
Active trials using JNJ-78278343
Found 6 active trials using this drug:
TrialFetch AI summary: Enrolling adults with metastatic castration-resistant prostate adenocarcinoma with bone and/or nodal metastases and no clear visceral metastases (on ongoing castration; PSA ≥2 ng/mL; ECOG 0–1). Participants receive IV pasritamig (JNJ-78278343), a KLK2×CD3 bispecific T-cell–redirecting antibody to drive T-cell–mediated tumor lysis, in combination with JNJ-86974680, an adenosine A2A receptor antagonist intended to relieve adenosine-mediated T-cell immunosuppression.
ClinicalTrials.gov ID: NCT07319871
TrialFetch AI summary: Adults with metastatic castration-resistant prostate adenocarcinoma on ongoing ADT (ECOG 0–1) who have progressed after 1–2 prior androgen receptor pathway inhibitors and are chemotherapy-naïve for prostate cancer are randomized to docetaxel (with prednisone) versus docetaxel plus pasritamig, an IV KLK2×CD3 bispecific T-cell–redirecting antibody designed to induce T-cell–mediated killing of KLK2-expressing prostate cancer cells. Treatment continues until confirmed radiographic progression or other protocol-defined discontinuation criteria.
ClinicalTrials.gov ID: NCT07225946
TrialFetch AI summary: Men with mCRPC limited to bone and/or nodes (no visceral disease) who have progressed after ARPI, two taxanes (unless not feasible), PSMA-lutetium if available/appropriate, and PARP inhibitor if BRCA-mutated receive pasritamig plus best supportive care versus placebo plus best supportive care. Pasritamig is an investigational KLK2×CD3 bispecific T‑cell–redirecting antibody designed to target prostate-restricted KLK2 and engage T cells; ongoing ADT required, ECOG 0–2.
ClinicalTrials.gov ID: NCT07164443
TrialFetch AI summary: Metastatic castration‑resistant prostate adenocarcinoma (ECOG 0–1; measurable or evaluable disease; PSA ≥2) treated with a combination of pasritamig (JNJ‑78278343), a KLK2×CD3 bispecific T‑cell–redirecting antibody, plus JNJ‑95298177 (ARX517), a PSMA‑targeted antibody–drug conjugate with a noncleavable microtubule inhibitor payload. Excludes prior KLK2‑directed therapy, recent T‑cell redirectors or checkpoint inhibitors, and prior PSMA radioligands for most expansion parts; aims to define an RP2CD and assess safety and preliminary activity.
ClinicalTrials.gov ID: NCT07082920
TrialFetch AI summary: Adults with metastatic castration‑resistant prostate adenocarcinoma (PCWG3; measurable/evaluable disease, PSA ≥2, on castration, ECOG 0–1; excludes active autoimmune disease requiring immunosuppression and recent major CV/CNS events) receive combination immunotherapy with pasritamig (KLK2×CD3 T‑cell–redirecting bispecific) plus JNJ‑87189401 (PSMA×CD28 costimulatory bispecific) to evaluate safety and preliminary activity. Suitable for mCRPC including those with small cell/neuroendocrine features (but not pure small cell/large cell NE).
ClinicalTrials.gov ID: NCT06095089
TrialFetch AI summary: Enrolls adults with metastatic prostate adenocarcinoma (mainly mCRPC after prior ARPI ± docetaxel; one cohort includes mHSPC with non-castrate testosterone and bone-only disease) to receive the KLK2×CD3 bispecific T‑cell engager pasritamig (JNJ‑78278343) combined with either cetrelimab (PD‑1 inhibitor), a taxane (docetaxel or cabazitaxel), or an ARPI (apalutamide, enzalutamide, darolutamide, or abiraterone/prednisone). Open-label cohorts assess safety and preliminary activity to define recommended regimens; ECOG 0–1 and measurable/evaluable disease required.
ClinicalTrials.gov ID: NCT05818683
