Phase 2 Randomized Study of JNJ-90301900 with Chemoradiation and Durvalumab in Stage III Unresectable NSCLC

The primary objective of this Phase 2 study is to evaluate the efficacy of **JNJ-90301900** as a radioenhancer when added to concurrent chemoradiation therapy (cCRT) followed by concurrent immunotherapy (cIT) in improving the objective response rate (ORR) in patients with locally advanced and unresectable Stage III non-small cell lung cancer (NSCLC). This is clinically relevant as enhancing the ORR could potentially lead to better clinical outcomes and improved survival rates in this patient population.

The clinical trial involves a total of **105 participants** diagnosed with **locally advanced and unresectable Stage III non-small cell lung cancer (NSCLC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a pathologically confirmed diagnosis of NSCLC and being candidates for standard care treatment involving concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab treatment. The trial population is characterized by an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1, indicating that participants are fully active or restricted in physically strenuous activity but ambulatory. Additionally, participants must have a life expectancy of at least six months at the time of consent. The study also considers vulnerable populations, ensuring comprehensive representation. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **Phase 2**, randomized, open-label, active-controlled study designed to evaluate the efficacy of **JNJ-90301900** in combination with chemoradiation followed by durvalumab in patients with locally advanced and unresectable Stage III non-small cell lung cancer (NSCLC). The primary objective is to determine whether JNJ-90301900, as a radioenhancer, can improve the objective response rate (ORR) in participants. The trial is expected to commence recruitment on April 5, 2025, and conclude by December 31, 2028.

Participants will be randomly assigned to receive either the investigational treatment or the control. The study will involve multiple visits, starting with a screening visit to confirm eligibility based on criteria such as a pathologically confirmed diagnosis of NSCLC, a target lesion amenable to intratumoral injection, and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. Following the screening, participants will undergo treatment visits where JNJ-90301900 is administered via **intratumoral injection** in conjunction with chemoradiation, followed by consolidation therapy with durvalumab.

Follow-up visits will be scheduled to monitor the participants' response to treatment and assess any adverse events. The end-of-study visit will occur after the completion of the treatment regimen and follow-up period, where final assessments will be conducted to evaluate the primary endpoint of ORR using Independent Central Review (ICR) assessments according to RECIST v1.1 criteria. The expected duration of participant involvement is approximately three years, with conditions for early termination including withdrawal of consent, significant adverse events, or disease progression.

The clinical trial involves the experimental medication **JNJ-90301900**, which is an **injection** formulation containing the active substance **hafnium oxide**. This compound is chemically synthesized and is utilized as a radioenhancer in the study. The administration route for JNJ-90301900 is **intratumoral use**, specifically targeting the tumor site. The dosing schedule is determined by the study protocol, with a maximum treatment period of 999 days. The dosage is measured in milligrams, although specific daily and total dose amounts are not predefined, allowing for flexibility based on individual participant needs and response. The product is developed by Janssen-Cilag International N.V. and is not formulated for pediatric use.

In addition to the experimental treatment, participants in the study receive standard-of-care therapy, which includes chemoradiation followed by durvalumab. This combination is part of the active-controlled design of the trial, serving as a comparator to evaluate the efficacy of JNJ-90301900. The standard-of-care regimen is administered according to established clinical guidelines for the treatment of locally advanced and unresectable Stage III non-small cell lung cancer (NSCLC). Compliance with the treatment protocol is monitored throughout the study to ensure adherence and to assess the impact of the experimental medication on the objective response rate (ORR) in participants.

Efficacy in this clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**, which will be evaluated using Independent Central Review (ICR) assessments according to RECIST v1.1 criteria. The ORR will be determined by the best response observed in participants with locally advanced and unresectable Stage III non-small cell lung cancer (NSCLC) who are treated with JNJ-90301900 in combination with chemoradiation followed by durvalumab. This trial aims to establish whether the addition of JNJ-90301900 as a radioenhancer can improve the ORR in this patient population.