Phase II Study of Rilvegostomig Immunotherapy With or Without Combination Chemotherapy in Unresectable Stage III NSCLC Receiving Concurrent Chemoradiotherapy

Primary objective: to assess safety and tolerability of immunotherapy, with or without other anticancer agents, in participants with unresectable stage III non‑small cell lung cancer; the outcome informs the risk‑benefit profile for integrating immunotherapy into concurrent chemoradiotherapy.

Secondary objectives include:

• Evaluation of efficacy by measuring progression‑free survival in the same patient population.
• Determination of objective response rate for induction therapy and overall response.
• Characterization of pharmacokinetics of the investigational immunotherapy.
• Investigation of immunogenicity where applicable.

Thirty‑nine participants with Non‑small Cell Lung Cancer were enrolled. The cohort included both male and female patients and encompassed individuals classified under age‑range codes 3 and 4, representing the adult population eligible for the study. All participants were required to have unresectable stage III disease confirmed histologically or cytologically, be eligible for concurrent chemoradiation with definitive platinum‑based cCRT to 60 Gy, and demonstrate an ECOG performance status of 0 or 1. Additional inclusion criteria mandated the absence of sensitizing EGFR mutations, ALK, ROS1, or RET rearrangements, documented tumor PD‑L1 expression with available tissue, at least one measurable target lesion per RECIST 1.1, and adequate organ and bone‑marrow function. Selection was based on multidisciplinary evaluation of resectability and staging according to IASLC v9.0 guidelines; vulnerable individuals were not excluded. No specific lifestyle restrictions such as diet or physical activity were stipulated in the provided information.

The study is a Phase II, open‑label, multicenter platform trial evaluating the safety and tolerability of the investigational agent rilvegostomig, administered alone or in combination with standard chemotherapeutic agents, in participants with unresectable Stage III Non-small Cell Lung Cancer scheduled for concurrent chemoradiotherapy. Eligible subjects undergo a screening visit to confirm histologic diagnosis, staging, PD‑L1 expression, organ function, and performance status; those meeting criteria are assigned to receive the investigational regimen alongside platinum‑based chemotherapy (cisplatin, carboplatin, pemetrexed, paclitaxel) and supportive agents (inflximab, mycophenolate mofetil). Treatment cycles are administered intravenously according to a predefined schedule, with concomitant radiotherapy delivered to a total dose of 60 Gy in 30 fractions. Follow‑up visits occur at the start of each treatment cycle for safety assessments, laboratory monitoring, and pharmacokinetic sampling, and imaging studies are performed per RECIST 1.1 at baseline, mid‑treatment, and at the end of treatment to evaluate response. After completion of chemoradiotherapy, participants enter a surveillance phase with visits every 8 weeks for up to 24 months, during which progression‑free survival, overall response rate, serum drug concentrations, and anti‑drug antibody status are recorded. The end‑of‑study visit concludes the trial-specific assessments. Participants remain in the study for an estimated total involvement of approximately two years. Early termination may occur for grade ≥ 3 treatment‑related adverse events, disease progression, withdrawal of consent, or failure to meet protocol‑defined compliance criteria.

The investigational agent Rilvegostomig is supplied as a solution for infusion and administered by intravenous infusion. The protocol specifies a dose of 00 mg per administration; the exact dosing schedule and frequency are defined in the trial regimen and recorded for each treatment cycle.

cisplatin is provided for intravenous administration at a dose of 75 mg/m² per infusion. It is given on designated days of the chemoradiotherapy schedule according to standard dosing intervals, and infusion details are documented in the study case report form.

pemetrexed is administered intravenously as an infusion. The dose is listed as 00 mg/m²; the specific amount and timing follow the protocol‑defined chemotherapy schedule, with administration recorded for compliance monitoring.

carboplatin is delivered by intravenous injection. The prescribed dose is 00 mg; dosing occurs on the same days as other chemotherapy agents per the study schedule, and infusion records are maintained.

paclitaxel is given intravenously. The protocol assigns a dose of 00 mg/m²; it is administered on scheduled chemotherapy days, and administration logs are used to verify adherence.

mycophenolate mofetil is taken orally. The dose is 00 g per day; dosing frequency is outlined in the study protocol, and pill counts are performed to assess participant compliance.

infliximab is administered as an intravenous infusion. The dose is 00 mg/kg; infusion timing follows the immunotherapy schedule, and infusion records are captured to ensure accurate delivery.

Efficacy will be evaluated using the following secondary endpoints: progression‑free survival (PFS), objective response rate (ORR), serum concentration of the immunotherapy agent, and the presence of anti‑drug antibodies (ADAs). PFS is defined as the time from treatment assignment/randomization or Cycle 1 Day 1 to radiological progression according to RECIST 1.1 or death from any cause in the absence of progression. ORR is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) per RECIST 1.1 for induction therapy or overall. Serum concentrations will be measured using validated pharmacokinetic assays, and ADAs will be detected and quantified with standard immunogenicity testing methods.

Radiological assessments will be performed using imaging modalities appropriate for RECIST evaluation. Blood samples for pharmacokinetic and immunogenicity analyses will be collected at predefined study visits in accordance with the protocol. Data will be analyzed using time‑to‑event methods for PFS and categorical analyses for ORR, concentration, and ADA status.