pasritamig (JNJ-8343) / J&J, Zymeworks - LARVOL DELTA

KLK2-PASenger: A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2030 ➔ Jun 2029

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Model-informed drug development (MIDD) to support dose selection of pasritamig, a KLK2xCD3 bispecific antibody, in patients with metastatic castration-resistant prostate cancer (mCRPC) (ESMO-IO 2025) - P1 | "No significant E-R relationship was identified for anemia and fatigue.Conclusions The MIDD supported the selected pasritamig target dose of 300 mg Q6W IV, preceded by 2 IV step-up doses of 3.5 mg on Day 1 and 18 mg on Day 8, for future studies. No dose-adjustment was warranted across subgroups investigated.Clinical trial identification NCT04898634.Legal entity responsible for the study Johnson & Johnson."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK2

CR108817: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=177 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Nov 2028 ➔ Oct 2027 | Trial primary completion date: Nov 2028 ➔ Oct 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

KLK2-PASenger: A Study of Pasritamig With Docetaxel Versus Docetaxel in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ADC & cellular therapies may transform prostate cancer. Phase 2s exist but there are 3 RIII trials as @PBarataMD states in this video. I-DXD vs docetaxel is the ADC R3. While 2 bispecifics RII (pasritamig targeting KLK-2 & Xaluritamig targeting STEAP-1) are ongoing @OncoAlert

Clinical

Pasritamig, a Differentiated, KLK2-Targeted T Cell Engager for Prostate Cancer (PCF 2025) - No abstract available

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK2

Pasritamig was recently granted Fast Track designation by the U.S. Food and Drug Administration. (J&J Press Release)

Fast track • Castration-Resistant Prostate Cancer

Translational analyses of T cell phenotypes and their association with clinical efficacy in the first-in-human (FIH) trial of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2025) - P1 | "Conclusions Biomarker analyses of peripheral and tumor-infiltrating T cells support the proposed mechanism of action of pasritamig and recommended RP2D. Pts with a higher percentage of reprogrammable progenitor T cells were more likely to have a PSA50 response."

Clinical • First-in-human • Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CASP3 • CD8 • KLK2

A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=216 | Recruiting | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Recruiting | Trial completion date: Feb 2026 ➔ Feb 2027

Enrollment open • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Study of JNJ-87189401 Plus JNJ-78278343 for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=130 ➔ 250

Enrollment change • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

KLK2-comPAS: A Study of Pasritamig Versus Placebo in Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P3 | N=663 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-78278343 in Combination With Either JNJ-63723283 (Cetrelimab), Taxane Chemotherapy, or Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=245 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=176 ➔ 245

Enrollment change • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

CR108817: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=247 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Aug 2028 ➔ Nov 2028

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

KLK2-comPAS: A Study of Pasritamig Versus Placebo in Late Line Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P3 | N=663 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CR108817: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=247 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Aug 2028 ➔ Nov 2028

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CR108817: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=247 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: May 2028 ➔ Aug 2028 | Trial primary completion date: May 2028 ➔ Aug 2028

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov) - P1 | N=110 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=216 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P1 | "Pre-medication with dexamethasone (16 mg) was required in SU and 1st TD...Pts had a median of 4 prior therapies (range 1-13; 99.4% ARPI, 78.2% taxane chemotherapy, 17.2% lutetium Lu 177 vipivotide tetraxetan)...In the RP2D safety population (n=45; 3.5 mg [Day 1], 18 mg [Day 8], 300 mg Q3W or Q6W IV), the most common TRAEs were infusion-related reactions (22.2%; Gr 1/2), fatigue (15.6%; Gr 1/2), and CRS (8.9%; all Gr 1, no tocilizumab was administered), no TRAEs led to treatment discontinuation, no ICANS was observed, and 2 serious TRAEs (Gr 1 CRS) were reported... Pasritamig was very well tolerated (<10% of pts experienced CRS [all Gr1] at the RP2D) with promising antitumor activity, demonstrating proof of concept for KLK2 as a target amenable to T-cell redirection. These results address an unmet need for a targeted T-cell based therapy that is safe to administer in an outpatient setting with clinically meaningful benefit in mCRPC. Phase 3 trials are planned."

Metastases • P1 data • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK2

Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Study. (PubMed, J Clin Oncol) - "Pasritamig demonstrated a favorable safety profile with very low rates of CRS and could be safely administered in an outpatient setting. Preliminary antitumor activity demonstrated proof of concept for KLK2 as a target in PC, warranting further development of pasritamig."

Journal • P1 data • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • KLK2

Johnson & Johnson unveils first-in-human results for pasritamig, showing early anti-tumor activity in prostate cancer (J&J Press Release) - P1 | N=260 | NCT04898634 | Sponsor: Janssen Research & Development, LLC | "Johnson & Johnson announced today new data from a Phase 1 study evaluating pasritamig (JNJ-78278343), a first-in-class bispecific antibody that activates T-cells to harness the body’s immune system against prostate cancer cells, showing promise in patients with advanced disease who have progressed after multiple lines of therapy....Of the patients in the RP2D efficacy group (n=33), treated once every six weeks, 42.4 percent achieved a 50 percent or greater reduction in their prostate-specific antigen (PSA) levels with a median rPFS of 7.9 months (95 percent confidence interval [CI] 2.9, not estimable [NE]) and 21.2 percent of patients continuing therapy. Treatment with pasritamig showed durable disease control and rPFS that compares favorably to historical data in heavily pretreated patients with mCRPC."

P1 data • Castration-Resistant Prostate Cancer

A Study of JNJ-78278343 in Combination With Either JNJ-63723283 (Cetrelimab), Taxane Chemotherapy, or Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=213 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

JNJ-8343: Data from P1 trial (NCT04898634) for advanced prostate cancer in 2025 (J&J) - 2025 Key Events

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer

CR108817: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer (clinicaltrials.gov) - P1 | N=257 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Sep 2027 ➔ May 2028 | Trial primary completion date: Sep 2027 ➔ May 2028

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor