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Comparing two treatments for advanced non-small cell lung cancer

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

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT06333678

This study is testing if switching from durvalumab to sotorasib can help people with advanced lung cancer live longer without their disease getting worse after standard treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment160 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionsdurvalumab, chemotherapy, radiation, durvlalumab
Locations11 sites (Miami, Florida and 10 other locations)
Trial IDNCT06333678 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of switching from durvalumab to sotorasib in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who have detectable minimal residual disease after chemoradiation. Participants will first undergo standard treatment and then be monitored for ctDNA levels before being randomized to either continue durvalumab or switch to sotorasib. The primary goal is to determine if the switch to sotorasib can improve progression-free survival compared to continuing durvalumab.

Who should consider this trial

Good fit: Ideal candidates are adults with locally advanced non-small cell lung cancer and a specific KRAS p.G12C mutation who have recently completed chemoradiation.

Not a fit: Patients with non-KRAS p.G12C mutations or those who do not have detectable minimal residual disease after treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with LA-NSCLC, potentially leading to longer disease control.

How similar studies have performed: Other studies have shown promising results with similar treatment approaches, but this specific combination is being evaluated for the first time.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Miami, Florida and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small Cell Lung CancerSotorasibDurvalumabLocally advanced diseaseKRAS p.G12C mutation22-321
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.