First data for sotorasib in patients with pancreatic cancer with <i>KRAS</i> p.G12C mutation: A phase I/II study evaluating efficacy and safety
Bibliographic record
Abstract
360490 Background: KRAS mutation is present in 90% of pancreatic ductal adenocarcinomas with p.G12C accounting for 1% to 2% of these mutations. Sotorasib, a small molecule that specifically and irreversibly inhibits KRASG12C, has been investigated in the CodeBreaK100 trial in patients with KRASG12C-mutated advanced solid tumors. Herein, we report on the largest dataset evaluating efficacy and safety of a KRASG12C inhibitor in patients with pretreated KRASG12C-mutated pancreatic cancer. Methods: CodeBreaK100 (NCT03600883) is an international, single arm, phase I/II study evaluating the efficacy and safety of sotorasib in patients with KRASG12C-mutated advanced solid tumors with ≥ 1 prior systemic therapy unless intolerant or ineligible for available therapies. The primary efficacy endpoint is confirmed objective response rate (ORR), assessed by blinded independent central review (BICR) per RECIST 1.1. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: As of November 1, 2021, 38 patients with pancreatic cancer (mean age: 65 years, 76.3% male) from the combined phase I/II study received sotorasib 960 mg once daily. Stage IV disease was present in 55.3% of patients at diagnosis, and in all patients at enrollment. Baseline ECOG scores were 0, 1, or 2 in 31.6%, 57.9%, and 10.5% of patients, respectively. Most patients (79%) had ≥ 2 prior lines of therapy (median: 2 [range: 1-8]). Median treatment duration was 4.1 months with a median follow-up of 16.8 months. Eight patients had confirmed partial response by BICR with a resulting ORR of 21.1% (95% CI: 9.55%-37.32%). DCR was 84.2% (Table 1). Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42.1%) patients. Grade ≥ 3 TRAEs occurred in 6 patients: diarrhea (2); fatigue (2); abdominal pain, ALT increase, AST increase, pleural effusion, and pulmonary embolism (1 each). No TRAEs were fatal or resulted in sotorasib discontinuation. Conclusions: Sotorasib demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRASG12C-mutated advanced pancreatic cancer, who have limited treatment options and poor prognosis. Clinical trial information: NCT03600883. [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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".