Status and phase
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About
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).
Full 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.
Enrollment
Sex
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Volunteers
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:
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:
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 durvalumab consolidation
Therapeutic Phase
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
160 participants in 2 patient groups
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Central trial contact
Narek Shaverdian, MD; Bob Li, MD
Data sourced from clinicaltrials.gov
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