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

NCT06333678 | Completed Phase 2 FDA Drug

• 1 other identifier: 22-321
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 10

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).

Conditions

Non-Small Cell Lung Cancer

Keywords

Sotorasib; Durvalumab; Locally advanced disease; KRAS p.G12C mutation; 22-321

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS will be defined as the time from randomization until progression or death , or from the time of randomization until the last follow up imaging (if no progression and alive). Progression will be evaluated by RECIST 1.1 guidelines.

  up to 3 years

Secondary Outcomes (1)

• Incidence of dose-limiting toxicity (DLT)

  1 month after starting Sotorasib

Study Arms (2)

continue standard of care (SOC) durvalumab treatment

ACTIVE COMPARATOR

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.

Drug: Durvalumab

switch sotorasib treatment until progression

EXPERIMENTAL

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.

Drug: Sotorasib

Interventions

Durvalumab DRUG

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

continue standard of care (SOC) durvalumab treatment

Sotorasib DRUG

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

switch sotorasib treatment until progression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (10)

University of Miami (Data Collection Only)

Miami, Florida, 33136, United States

Location

University of Michigan (Data Collection Only)

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

Location

Vanderbilt University (Data Collection Only)

Nashville, Tennessee, 37232, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Narek Shaverdian, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II randomized trial

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 27, 2024
• Study Start: March 20, 2024
• Primary Completion: January 27, 2026
• Study Completion: January 27, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (10)