Inclusion Criteria:

• Part 1: Individuals with a diagnosis of locally advanced or metastatic disease (solid tumors except tumors of the central nervous system [CNS]) who have previously received available standard therapy and progressed, or cannot tolerate standard therapy, or for whom there is no standard of care per regional guidelines

• Part 2 Cohort A: Individuals with histologically or cytologically confirmed metastatic tumors of adenocarcinoma or squamous cell carcinoma histology, for which any platinum-based systemic regimen is considered a standard of care (per national comprehensive cancer network [NCCN] guidelines) and whose disease has progressed after standard therapy

• Eastern cooperative oncology group performance status (ECOG) performance status of Grade 0 or 1

• Part 2 Cohort A participants planned to receive optional cetrelimab (participants not meeting this criterion may still be enrolled in the study but cannot receive cetrelimab): Thyroid function laboratory values within normal range except for participants on thyroid hormone replacement therapy

• A participant of childbearing potential must practice at least 2 highly effective methods of contraception throughout the study and through 14 months (for women) and 11 months (for men) after the last dose of JNJ-1761981 or 5 months after the last dose of cetrelimab or other anti-PD(L)1 treatment, whichever is later

Exclusion Criteria:

• Active symptomatic disease involvement of the central nervous system

• Prior or concurrent second malignancy (other than the disease under study) that due to natural history or treatment is likely to interfere with any study endpoints of safety or the antitumor activity of the study treatment(s)

• Active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures

• Known allergies, hypersensitivity, or intolerance to JNJ-1761981 or its excipients

• Lesions invading or adjacent to major blood vessels or other critical structures (for example, airways) not suitable for injection

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 09/10/2026. Questions regarding updates should be directed to the study team contact.