A Study of JNJ-86974680 in Participants With Advanced Non-small Cell Lung Cancer

August 27, 2026 updated by: Johnson & Johnson Enterprise Innovation Inc.

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

The purpose of this study is to determine a safe and tolerable dose(s) of JNJ-86974680 for further research in combination with cetrelimab and radiation therapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Study consists of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion), post-treatment follow-up period, and long-term extension period.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 12203
        • Charite Research Organisation GmbH
      • Giessen, Germany, 35392
        • Universitaetsklinikum Giessen und Marburg GmbH
  • South Korea
      • Seoul, South Korea, 03722
        • Severance Hospital Yonsei University Health System
      • Seoul, South Korea, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08028
        • Hosp. Univ. Quiron Dexeus
      • Barcelona, Spain, 8035
        • Hosp Univ Vall D Hebron
      • Madrid, Spain, 28041
        • Hosp. Univ. 12 de Octubre
      • Valencia, Spain, 46026
        • Hosp. Univ. I Politecni La Fe
  • United States
    • Georgia
      • Newnan, Georgia, United States, 30265
        • City of Hope 1
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14203
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • NEXT Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Individuals with histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer (NSCLC)
  • Part 1: NSCLC with a known actionable genetic mutation (for example, epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], c-ros oncogene 1 [ROS1], v-raf murine sarcoma viral oncogene homolog B1 [BRAF]) must have received all approved targeted therapies and have progressed
  • Part 2: No targetable mutations (for example, EGFR [epidermal growth factor receptor], ALK [anaplastic lymphoma kinase], ROS1[c-ros oncogene 1], and BRAF [B-Raf proto-oncogene, serine/threonine kinase])
  • Part 1 and Cohort A of part 2: Must have been treated with (a) anti-programmed death protein 1 (anti-PD-1) or programmed cell death ligand 1 (PD-L1) therapy and (b) platinum-based chemotherapy
  • For Cohort B of Part 2: Previously treated with anti-PD-1/PD-L1 therapy for metastatic disease as the prior line of therapy
  • For Cohort C of Part 2: Treatment naïve
  • Adequate organ function

Exclusion Criteria:

  • Active central nervous system (CNS) disease involvement
  • Active autoimmune disease
  • Active infection
  • History of solid organ or hematologic stem cell transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: JNJ-86974680+Cetrelimab
Participants will receive JNJ-86974680 alone (dose 1, dose 2, dose 3, and dose 4) daily in 4 cohorts and then along with a set dose of cetrelimab.
Drug: JNJ-86974680
JNJ-86974680 will be administered.
Drug: Cetrelimab
Cetrelimab will be administered.
Experimental: Part 2: JNJ-86974680+Cetrelimab+Radiation Therapy (RT)
Part 2 will consist of 3 cohorts (A, B and C) and participants will receive treatment with the selected dose of JNJ-86974680 in combination with cetrelimab from part 1, in conjunction with radiation.
Drug: JNJ-86974680
JNJ-86974680 will be administered.
Drug: Cetrelimab
Cetrelimab will be administered.
Radiation: Radiation Therapy
Radiation therapy 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
Time Frame: Up to 2 years 5 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE 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 5 months
Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame: Up to 2 years 5 months
The DLTs are specific adverse events and are defined as any of the following: non-hematologic toxicity and hematological toxicity.
Up to 2 years 5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of JNJ-86974680
Time Frame: Up to 2 years 5 months
Cmax is defined as maximum observed plasma concentration of JNJ-86974680.
Up to 2 years 5 months
Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC0-t) of JNJ-86974680
Time Frame: Up to 2 years 5 months
(AUC0-t) is defined as area under the plasma concentration of JNJ-86974680 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t).
Up to 2 years 5 months
Part 2: Overall Response Rate (ORR)
Time Frame: Up to 2 years 5 months
ORR is defined as the percentage of participants who have a best response of complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) version (v)1.1, maintained for at least 4 weeks.
Up to 2 years 5 months
Part 2: Complete Response Rate (CRR)
Time Frame: Up to 2 years 5 months
CRR is defined as the proportion of participants with a best response of CR.
Up to 2 years 5 months
Part 2: Duration of Response (DOR)
Time Frame: Up to 2 years 5 months
DoR is defined as the time from the date of first initial documentation of a response to the date of first documented evidence of progression of disease according to immunotherapy response evaluation criteria in solid tumors (iRECIST) or death due to any cause, whichever occurs first.
Up to 2 years 5 months
Part 2: Disease Control Rate (DCR)
Time Frame: Up to 2 years 5 months
DCR is defined as the percentage of participants who achieve a best of response of PR, CR, or stable disease using RECIST v1.1.
Up to 2 years 5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johnson & Johnson Enterprise Innovation Inc.

Investigators

  • Study Director: Johnson & Johnson Enterprise Innovation, Inc Clinical Trial, Johnson & Johnson Enterprise Innovation Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 27, 2023

Primary Completion (Estimated)

April 14, 2027

Study Completion (Estimated)

June 7, 2029

Study Registration Dates

First Submitted

October 31, 2023

First Submitted That Met QC Criteria

October 31, 2023

First Posted (Actual)

November 3, 2023

Study Record Updates

Last Update Posted (Actual)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 86974680NSC1001 (Janssen Research & Development, LLC)
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2023-506393-12-00 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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