The purpose of this study is to determine whether JNJ-90301900 added to concurrent platinum-based doublet chemotherapy with radiation therapy (cCRT) followed by consolidation immunotherapy (cIT) can improve objective response rate (ORR; that is percentage of participants whose best response is complete response or partial response during the study) in participants with locally advanced and unresectable stage III non-small cell lung cancer.

Inclusion Criteria:

• Must be a candidate for standard of care (SOC) treatment of non small cell lung cancer (NSCLC) by concurrent platinum-based doublet chemotherapy with radiation therapy (cCRT) followed by consolidation durvalumab treatment as determined by the investigator and per local guidelines at screening
• Have a medical history of pathologically (histologically or cytologically) proven diagnosis of NSCLC within 3 months prior to enrollment/randomization
• Have locally advanced unresectable stage III NSCLC according to the eighth edition lung cancer stage classification
• Have at least 1 target lesion (primary lung lesion or involved lymph node[s]) per RECIST version 1.1 that is amenable to intratumoral and/or intranodal injection and intensity modulated radiation therapy (IMRT) as determined by the investigator at screening
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Medical history of: (a) Primary immunodeficiency (b) Organ transplant that requires therapeutic immunosuppression
• Any of the following within 3 months prior to enrollment/randomization: severe or unstable angina, myocardial infarction, clinically significant ventricular arrhythmias or heart failure New York heart association functional classification class III to IV
• Another concurrent or prior primary malignancy within the last 36 months at informed consent
• Known allergies, hypersensitivity, or intolerance to any ingredients of JNJ-90301900 crystalline solution, platinum-based doublet chemotherapy (ChT), or durvalumab
• History of coagulation disorders, including: (a) Active bleeding diathesis or requirement for therapeutic anticoagulation or antiplatelet that cannot be interrupted or altered for JNJ-90301900 injection procedures, (b) Major thromboembolic events (for example, pulmonary embolism, cerebrovascular accident) within 3 months of enrollment or randomization

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.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.