Sotorasib plus panitumumab for pre-treated non-small cell lung cancer with <i>KRAS</i>G12C mutation: A phase 1b study.
Bibliographic record
Abstract
8559 Background: Sotorasib, a selective and irreversible KRASG12C inhibitor, is approved for treatment of adults with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) who received ≥ 1 prior systemic therapy. EGFR pathway alterations have been observed as an acquired resistance mechanism with sotorasib monotherapy. Treatment with sotorasib plus an EGFR inhibitor, such as panitumumab, may enhance efficacy over sotorasib monotherapy, as demonstrated in chemotherapy refractory metastatic colorectal cancer. Our current study assesses sotorasib plus panitumumab in pre-treated advanced NSCLC. Methods: Key eligibility criteria for this dose expansion cohort of the CodeBreaK 101 study (NCT04185883) included advanced NSCLC positive for KRAS G12C, ≥ 1 prior treatment for advanced disease, and no prior KRASG12C inhibitor exposure. Patients (pts) with active brain metastases were excluded. Primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), progression free survival (PFS), as well as overall survival (OS). Results: As of January 11, 2024, 40 pts (median age, 67.5 years; 55% female) received oral sotorasib 960 mg daily and panitumumab IV 6 mg/kg every 2 weeks. 43% of pts had a history of brain metastases. Median number of prior lines of therapy was 1; 42% received ≥ 2 regimens and 38% had disease progression as their best response to last line of therapy. Most pts received anti-PD-(L)1 therapy (90%), platinum-based chemotherapy (85%), or both (78%). Most common (> 30%) treatment-related adverse events (TRAEs) attributed to any study drug were: diarrhea in 19 (48%) pts, dermatitis acneiform in 18 (45%), and dry skin in 16 (40%). Most common grade ≥ 3 TRAEs were increased ALT and AST in 7 (18%) and 4 (10%) pts, respectively, dermatitis acneiform in 5 (13%), diarrhea in 3 (8%), and hypomagnesaemia in 2 (5%) pts. Overall response rate was 45% (all partial responses), with a DCR of 90% (Table). Median PFS was 5.8 months (median follow-up 14.0 months). At a median follow-up of 11.0 months, OS data were not yet mature. Conclusions: This cohort of sotorasib plus panitumumab in pre-treated patients with KRAS G12C advanced NSCLC demonstrated safety consistent with each drug's profile. The ORR appears promising in this pretreated population and may warrant further investigation. Clinical trial information: NCT04185883 . [Table: see text]
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".