Cetrelimab

Shows activity

Also known as:

JNJ-63723283

Cancer types include:

non-small cell lung cancer prostate cancer small cell lung cancer

HealthScout AI Analysis

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Overview

Cetrelimab (JNJ-63723283) is an investigational human IgG4 monoclonal antibody targeting PD‑1. Early phase studies show antitumor activity and a safety profile broadly consistent with approved PD‑1 inhibitors across multiple solid tumors. Cetrelimab is also being studied in bladder cancer both as monotherapy and in combinations (e.g., with the intravesical gemcitabine-releasing system TAR‑200 and with the FGFR inhibitor erdafitinib). (ascopubs.org)

Mechanism of action

Cetrelimab binds PD‑1 with high affinity, blocks interaction with PD‑L1/PD‑L2, and restores T‑cell function in vitro; it shows antitumor activity in mouse and patient-derived xenograft models. Reported KD for human PD‑1 is ~1.7 nM, with ligand blocking and T‑cell cytokine induction demonstrated preclinically. (pmc.ncbi.nlm.nih.gov)

Efficacy

First‑in‑human, phase 1/2 (LUC1001; NCT02908906): Among 156 response‑evaluable patients with various advanced cancers, overall response rate (ORR) was 15% (2 CR, 22 PR). Tumor‑specific ORR included 26% in NSCLC (42% in PD‑L1 ≥50%), 25% in melanoma (28% in non‑uveal melanoma), 50% in renal cancer (1/2), 8% in MSI‑H/dMMR CRC, and 14% in gastric/esophageal cancer; no responses were seen in small cohorts with bladder cancer (n=4) or SCLC (n=10). (ascopubs.org)
Urothelial carcinoma—NORSE phase 2 (erdafitinib ± cetrelimab) in treatment‑naïve, cisplatin‑ineligible, FGFR‑altered metastatic disease: Final ASCO 2023 abstract reported the randomized comparison; public summaries indicate ORR 54.5% with erdafitinib+cetrelimab (6 CRs) vs 44.2% with erdafitinib alone, and median PFS 10.97 months vs 5.62 months, respectively. (Note: details come from conference abstract and peer‑reviewed meeting reports/reviews.) (ascopubs.org)
Non–muscle‑invasive bladder cancer (NMIBC)—SunRISe‑1 phase 2b: Early AUA 2023 results showed a centrally confirmed complete response (CR) rate of 38% with cetrelimab monotherapy in BCG‑unresponsive high‑risk NMIBC with CIS; TAR‑200 monotherapy cohorts in the same study achieved higher CR rates, but cetrelimab monotherapy served as a comparator. (auajournals.org)
Muscle‑invasive bladder cancer (MIBC)—SunRISe‑4 phase 2 (neoadjuvant): Interim ESMO 2024 presentation/press release reported pathologic complete response (pCR) 42% with TAR‑200+cetrelimab vs 23% with cetrelimab alone before cystectomy in cisplatin‑ineligible/refusing patients. (Company release; full peer‑reviewed data pending.) (jnj.com)
Muscle‑invasive bladder cancer—SunRISe‑2 phase 3 (organ‑preserving setting): The trial of TAR‑200+cetrelimab vs chemoradiation was discontinued after a pre‑specified interim analysis for not demonstrating superiority over chemoradiation. (jnj.com)

Safety

In the phase 1/2 LUC1001 study (all doses, multiple tumor types), common adverse events included asthenia (19%), fatigue (19%), dyspnea (16%), and diarrhea (16%). Grade ≥3 AEs occurred in 45% of patients (most commonly anemia 6%, dyspnea 4%); immune‑related AEs occurred in 30% (any grade) and 7% (grade ≥3). Safety and activity were described as consistent with approved PD‑1 inhibitors. (ascopubs.org)
Early dose‑escalation (phase 1) reported one DLT (grade 3 pleural effusion) at 240 mg Q2W; immune‑related AEs were mostly grade 1–2. The recommended phase 2 dose was 240 mg Q2W. (ascopubs.org)
In urothelial carcinoma combinations (NORSE), conference reports describe an acceptable safety profile for erdafitinib+cetrelimab consistent with component agents; detailed peer‑reviewed safety data are limited in the public domain. (ascopubs.org)

Notes on development status

Cetrelimab is being studied primarily in bladder cancer programs (SunRISe) as monotherapy and with TAR‑200, and in combination with erdafitinib in FGFR‑altered urothelial carcinoma. The phase 3 organ‑preserving MIBC study (SunRISe‑2) closed for futility, while phase 2 programs (e.g., SunRISe‑4 neoadjuvant) continue. (jnj.com)

Active trials using Cetrelimab

Found 3 active trials using this drug:

A Phase 1b, Two-Part Study of Tolododekin Alfa (ANK-101) in Combination With an Anti-PD-1/PD-L1 Antibody in Participants With Advanced Non-Small Cell Lung Cancer

Sponsor: Ankyra Therapeutics, Inc (industry) Phase: 1 Start date: Sept. 30, 2025

HealthScout AI summary: Adults with advanced/metastatic NSCLC (ECOG 0–1), excluding EGFR/ALK alterations, receive intratumoral tolododekin alfa (ANK-101), an anchored IL‑12 designed for localized immune activation, combined with an anti–PD-1/PD-L1 antibody. Includes two cohorts: post–PD-1/PD-L1 and platinum–pretreated patients receiving tolododekin alfa plus cetrelimab, and treatment‑naïve patients receiving tolododekin alfa plus investigator’s choice of approved PD-1/PD-L1 inhibitor; mandatory fresh biopsies.

ClinicalTrials.gov ID: NCT07027514

A Phase 1 Study of JNJ-86974680, an A2a Receptor Antagonist, Administered as Monotherapy and in Combination With Cetrelimab and Radiotherapy for Advanced Non-small Cell Lung Cancer

Sponsor: Johnson & Johnson Enterprise Innovation Inc. (industry) Phase: 1 Start date: Nov. 27, 2023

HealthScout AI summary: This trial enrolls adults with stage IIIB-IV NSCLC, including patients who have progressed on standard therapies (and some treatment-naïve), to evaluate JNJ-86974680—an investigational adenosine A2A receptor antagonist—given alone or in combination with the PD-1 inhibitor cetrelimab and, in later cohorts, radiotherapy. Excludes patients with active CNS disease, autoimmune conditions, significant infection, or prior transplant.

ClinicalTrials.gov ID: NCT06116786

A Phase 1b Study of JNJ-78278343, a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With Either JNJ-63723283 (Cetrelimab), Taxane Chemotherapy, or Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer

Sponsor: Janssen Research & Development, LLC (industry) Phase: 1 Start date: April 26, 2023

HealthScout 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