Registrational phase 2 trial of sotorasib in KRAS p. G12C mutant NSCLC: first disclosure of the CodeBreaK 100 primary analysis
Bibliographic record
Abstract
Background: Approximately 13% of patients with lung adenocarcinomas harbor KRAS p. G12C mutation. Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRAS G12C . Methods: This international, single-arm, phase 2 study evaluated the efficacy and safety of sotorasib, administered orally once daily at 960 mg, in the cohort of patients with locally advanced or metastatic KRAS p. G12C mutant NSCLC. Key inclusion criteria: centrally confirmed KRAS p. G12C; progression on anti-PD-1/PD-L1 immunotherapy and/or platinum-based combination chemotherapy; and ≤ 3 prior lines of therapy. Patients with untreated active brain metastases were excluded. Results: Data cutoff was September 1, 2020. A total of 126 patients were enrolled and received at least 1 dose of sotorasib. Median follow-up time on study was 9.3 months (range: 1.1 + to 12.2). Median age was 63.5 years (range: 37 to 80), and 117 (92.9%) were former or current smokers. 72 (57.1%) patients received 2 or 3 prior lines of anticancer therapy. 91.3% received anti-PD-1/PD-L1 immunotherapy, and 81.0% received both platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. Per central review, 123 patients had at least 1 measurable lesion at baseline and were evaluated for efficacy. 46 patients experienced a confirmed response (2 complete responses and 44 partial responses), resulting in an ORR of 37.4% (95% Cl: 28.8 – 46.6). At a median follow-up of 6.9 months for DoR, 52.2% of responders remained on treatment without progression. DCR was 80.5% (95% Cl: 72.4 – 87.1). Median PFS was 6.7 months (95% Cl: 4.9 – 8.1). Treatment-related adverse events (TRAEs) of any grade occurred in 88 (69.8%) patients and led to discontinuation in 9 (7.1%) patients. Grade ≥ 3 TRAEs were reported in 26 (20.6%) patients; those that occurred in > 3% of patients were alanine aminotransferase increase (8/126, 6.3%), aspartate aminotransferase increase (7/126, 5.6%), and diarrhea (5/126, 4.0%). No fatal TRAEs were reported. Conclusions: In the phase 2 CodeBreaK 100 trial, sotorasib provided deep responses and durable clinical benefit with a favorable safety profile in patients with pretreated NSCLC harboring KRAS p. G12C, validating the previous phase 1 results. Publication History Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.017 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".