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

NCT ID: NCT06333678

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-20
• Study Completion Date: 2027-03-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

continue standard of care (SOC) durvalumab treatment

Will continue to receive durvalumab, 10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.

Group Type: ACTIVE_COMPARATOR

Durvalumab

Intervention Type: DRUG

10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.

switch sotorasib treatment until progression

Will receive sotorasib at 960 mg daily until progression. A dose de-escalation regimen based on toxicity will be implemented as below. If 120 mg cannot be tolerated, sotorasib will be discontinued and the patient will be removed from the trial.

Group Type: EXPERIMENTAL

Sotorasib

Intervention Type: DRUG

960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.

Interventions

Durvalumab

10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.

Intervention Type: DRUG

Sotorasib

960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Pre-Monitoring Phase

• Histologic diagnosis of NSCLC
• Locally advanced disease, defined as AJCC 8th Edition Stage III disease.
• Plan for, currently receiving, or recently completed definitive chemoradiation. Definitive radiation is defined as 56-70 Gy in 28-35 fractions concurrently with one of the following chemotherapy regimens:

• Carboplatin + pemetrexed
• Cisplatin + pemetrexed
• Paclitaxel + carboplatin
• Cisplatin + etoposide
• KRAS p.G12C mutation identified through molecular testing
• Adequate hepatic function, with adequate function defined as AST and ALT < 2.5 x the upper limit of normal (ULN)
• Patient eligible for consolidative durvalumab therapy
• ECOG Performance status 0 - 2.
• Age ≥ 18 years.
• Patients must have decision-making capacity to consent to the study.
• Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: >/= 55 years old and no menses for 1> year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral salpingectomy OR history of bilateral oophorectomy) or must be willing to comply with contraception requirements.

Monitoring Phase

• Completed definitive chemoradiation. Definitive radiation is defined as 56-70 Gy in 28-35 fractions concurrently with one of the following chemotherapy regimens:

• Carboplatin + pemetrexed
• Cisplatin + pemetrexed
• Paclitaxel + carboplatin
• Cisplatin + etoposide
• Detectable ctDNA measured within 8 weeks (+2 weeks) of completing definitive chemoradiation
• No evidence of radiographic progression, as measured through SOC imaging, as deemed by principal investigator, including a CT scan of the chest
• ECOG Performance status 0 - 2.
• Plan to start or already started durvalumab consolidation

Therapeutic Phase

• No evidence of radiographic RECIST 1.1 progression, as measured through SOC imaging, as deemed by principal investigator, including a CT scan of the chest
• MRD as measured by ctDNA testing (described above)
• Candidate for sotorasib therapy
• Must have a negative pregnancy test (serum or urine) within 3 days prior to the first dose of sotorasib (if assigned to Group 2).

Exclusion Criteria

• Serious medical co-morbidities precluding radiotherapy, determined at the discretion of the treating investigator.
• Pregnant or lactating women.
• Physical limitation to undergo radiotherapy.
• Other active malignancy (e.g. receiving active treatment) within the last year except for basal cell carcinoma of the skin and in situ malignancy even if without evidence of disease and patients on adjuvant hormonal therapies (e.g. breast, prostate), or bladder cancer with localized diseases
• Prior pneumonitis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Narek Shaverdian, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

University of Miami (Data Collection Only)

Miami, Florida, United States

University of Michigan (Data Collection Only)

Ann Arbor, Michigan, United States

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, United States

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, United States

Vanderbilt University (Data Collection Only)

Nashville, Tennessee, United States

Countries

United States

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

22-321

Identifier Type: -

Identifier Source: org_study_id