Updated analysis of the efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic <i>NTRK</i> fusion-positive (<i>NTRK</i>-fp) solid tumors.
Bibliographic record
Abstract
3099 Background: NTRK gene fusions, coding for chimeric TRK proteins, are oncogenic drivers in many solid tumors. In an integrated analysis of three phase 1/2 trials (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]), entrectinib, a potent CNS-active TRK inhibitor, showed durable systemic and intracranial responses in pts with NTRK-fp solid tumors. We report updated data from a larger cohort with longer follow-up (clinical cutoff 2 Aug 2021). Methods: Pts with locally advanced/metastatic NTRK-fp solid tumors and ≥12 months’ follow-up from first tumor assessment were efficacy evaluable. The safety cohort also included pts from TAPISTRY (NCT04589845). Tumor responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every 8 weeks thereafter. Primary endpoints: objective response rate (ORR) and duration of response (DoR). Progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR and safety were also assessed. Results: The efficacy-evaluable cohort comprised 150 adults (vs 121 previously) with 17 different solid tumor types. Median age was 58.5 years; 91% of pts had ECOG PS 0–1 and 37% had received ≥2 prior lines of therapy. Median survival follow-up was 30.6 months. ORR was 61.3% (n = 92/150; 95% CI: 53.1–69.2), including 25 complete responses. Responses were observed in all tumor types with n>1 (Table). Median DoR, PFS and OS were 20.0 months (95% CI 13.2–31.1), 13.8 months (95% CI 10.1–20.0), and 37.1 months (95% CI 27.2–not estimable [NE]), respectively. In pts with and without investigator-assessed baseline CNS metastases (n = 31 / n = 119), ORR was 61.3% (95% CI 42.2–78.2) and 61.3% (95% CI 52.0–70.1) respectively. IC-ORR was 69.2% (n = 9/13) in pts with BICR-assessed measurable CNS metastases; median IC-DoR was 17.2 months (7.4–NE). In the safety population (N = 235: all treated pts), most treatment-related adverse events (TRAEs) were grade 1/2 and not serious; the most frequent were dysgeusia (36.6%), diarrhea (29.8%) and weight increase (28.5%). TRAEs led to dose interruption, reduction and discontinuation in 32.8%, 24.3% and 7.2% of pts, respectively. Conclusions: In this updated analysis, entrectinib continued to demonstrate deep and durable responses and was well tolerated in pts with NTRK-fp solid tumors with or without baseline CNS metastases. Clinical trial information: STARTRK-2 [NCT02568267]. [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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".