NCT06333678

A Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)

A Randomized Phase II Study of Sotorasib Versus Continued Consolidation Durvalumab in Patients With KRAS G12C Mutant Locally Advanced Non-small Cell Lung Cancer (LANSCLC) With Persistent ctDNA Defined Minimal Residual Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Memorial Sloan Kettering Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, the researchers will look at whether having participants switch from durvalumab to sotorasib when they have detectable minimal residual disease (MRD) is an effective treatment approach for locally advanced non-small cell lung cancer (LA-NSCLC). The researchers will see whether this switch to sotorasib can control LANSCLC longer compared to the treatment approach of staying on durvalumab (and not switching to sotorasib).

Detailed description

In the first phase of the randomized trial, defined as the Pre-Monitoring Phase, patients with LANSCLC with a KRAS G12C mutation who are planned to undergo, are undergoing, or very recently completed definitive chemoradiation with the plan for durvalumab consolidation are enrolled. Chemoradiation treatment and all clinical assessments during the Pre-Monitoring Phase are per standard of care as per institutional standards. Patients who (1) complete chemoradiation, (2) have detectable ctDNA post chemoradiation, (3) are without evidence of progressive disease on imaging, (4) and are planned to start durvalumab consolidation then continue into the Monitoring Phase. All other patients are no longer on trial and are taken off study. Patients in the Monitoring Phase will have ctDNA measured again early-on during durvalumab consolidation (i.e. cycle 3 of durvlalumab +/- 2 weeks) in conjunction with standard of care imaging. Patients with MRD will then continue to the Randomization Phase of trial. In the Randomization Phase patients will be randomized in a 1:1 fashion to continue standard of care durvalumab (group 1) vs. switch to sotorasib at 960 mg daily (group 2), with the primary endpoint of PFS. Patients switching to sotorasib will undergo a 28-day durvalumab washout and will receive sotorasib at 960 mg daily until progression. Washout will be confirmed by ensuring that cycle 1, day 1 of sotorasib is scheduled for at least 28 days after the most recent durvalumab dose.

Conditions

• Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab	10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.
DRUG	Sotorasib	960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.

Timeline

• Start date: 2024-03-20
• Primary completion: 2026-01-27
• Completion: 2026-01-27
• First posted: 2024-03-27
• Last updated: 2026-01-29

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study