MSK 22-321

Full Name

MSK 22-321: A Randomized Phase II Study of Sotorasib versus Continued Consolidation Durvalumab in Patients with KRAS G12C Mutant Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) with Persistent ctDNA Defined Minimal Residual Disease

Eligibility

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