A Study of JNJ-95437446 in Participants With Advanced-Stage Solid Tumors

A Phase 1 Study of JNJ-95437446 in Participants With Advanced-Stage Solid Tumors

The purpose of this study is to determine recommended phase 2 doses (RP2Ds) of JNJ-95437446 in Part 1, and to further evaluate the safety of the RP2Ds in participants with advanced solid tumors in Part 2.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: JNJ-95437446

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital Yonsei University Health System
• Spain
  • Barcelona, Spain, 8035
    • Recruiting
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hosp Univ Hm Sanchinarro
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have been previously diagnosed with histologically confirmed unresectable, locally advanced, or metastatic non-small cell lung cancer, colorectal carcinoma, or head and neck squamous cell carcinoma
• Participants with non-small cell lung cancer (NSCLC) adenocarcinoma and colorectal cancer (CRC) must have local molecular testing to determine epidermal growth factor receptor (EGFR) mutational status for NSCLC and Kirsten rat sarcoma/neuroblastoma ras viral oncogene/v-raf murine sarcoma oncogene B1 (KRAS/NRAS/BRAF) mutation status for CRC
• Have measurable or evaluable disease:
• Part 1: Either measurable or evaluable disease; Part 2: At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version (v) 1.1
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1 at screening
• Participants must have appropriate hematologic, renal, and hepatic function within the required limits

Exclusion Criteria:

• Any prior medical history of ILD/pneumonitis, including pneumonitis from anti-PD-1/ PD-L1 antibody or radiation that required systemic steroids
• Toxicity from prior anticancer therapy that has not resolved to Grade <=1
• Evidence of clinically significant active viral, bacterial, or fungal infection within 7 days before the first dose of study treatment requiring systemic or non-topical treatment
• History of clinically significant cardiovascular disease within 6 months prior to signing informed consent
• Participants with prior or concurrent second malignancy cannot be enrolled if prior/concurrent malignancy's natural history of treatment is likely to interfere with any safety or efficacy study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-95437446; Participants will receive JNJ-95437446 in Part 1 until at least two recommended phase 2 doses (RP2Ds) has been developed. Participants in Part 2 will receive JNJ-95437446 at the RP2Ds developed in Part 1.	Drug: JNJ-95437446; JNJ-95437446 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) by Severity	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product and does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.	Up to 2 years and 4 months
Part 1: Number of Participants with Dose-Limiting Toxicity (DLT)	The DLTs are specific adverse events that includes high grade hematologic or non-hematologic toxicities with exceptions and/or toxicities leading to treatment discontinuation.	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate (ORR) is defined as the percentage of participants who have best response of complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST).	Up to 2 years and 4 months
Duration of Response (DOR)	DOR is defined for the responders from the date of initial documentation of a response to the date of first documented evidence of disease progression according to RECIST version (v.) 1.1, or death due to any cause, whichever occurs first.	Up to 2 years and 4 months
Progression Free Survival (PFS)	PFS is defined as the time from the first dose of JNJ-95437446 to either progressive disease (PD) or death due to any cause, whichever comes first.	Up to 2 years and 4 months
Maximum Plasma Concentration (Cmax) for JNJ-95437446	Serum samples will be analyzed to determine Cmax of JNJ-95437446 antibody-drug conjugate, total antibody, released payload and the payload's metabolite.	Up to 2 years and 4 months
Time to Reach Cmax (Tmax) for JNJ-95437446	Tmax defined as the the time to reach maximum observed plasma concentration of JNJ-95437446 antibody-drug conjugate, total antibody, released payload and the payload's metabolite will be reported.	Up to 2 years and 4 months
Area Under the Plasma Concentration - Time (AUC [0-t]) Curve for JNJ-95437446 antibody-drug conjugate, total antibody, released payload and the payload's metabolite.	AUC (0-t) defined as area under the plasma concentration-time curve during a dosing interval of JNJ-95437446 antibody-drug conjugate, total antibody, released payload and the payload's metabolite will be reported.	Up to 2 years and 4 months
Number of Participants With Anti JNJ-95437446 Antibodies	Serum samples will be analyzed for the detection of anti-JNJ-95437446 antibodies using a validated assay method.	Up to 2 years and 4 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2025
• Primary Completion (Estimated): November 18, 2027
• Study Completion (Estimated): April 24, 2028

Study Registration Dates

• First Submitted: August 5, 2025
• First Submitted That Met QC Criteria: August 5, 2025
• First Posted (Actual): August 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 95437446LUC1001 (Other Identifier: Janssen Research & Development, LLC); 2025-521535-36-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes