Abstract PR003: Repotrectinib in patients with <i>ROS1</i> fusion-positive (<i>ROS1</i>+) non-small cell lung cancer (NSCLC): Update from the pivotal phase 1/2 TRIDENT-1 trial
Notice bibliographique
Résumé
Abstract Introduction: Repotrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), has demonstrated durable activity and manageable safety in patients (pts) with locally advanced/metastatic ROS1+ NSCLC in the pivotal phase 1/2 TRIDENT-1 trial (NCT03093116). We report efficacy with a minimum follow-up of 14 months (mo) from start of treatment in two ROS1+ NSCLC primary efficacy cohorts and safety in all pts treated at the recommended phase 2 dose (RP2D). Methods: Pts with ROS1+ NSCLC were assigned to 4 cohorts by treatment history: TKI-naïve, 1 TKI and no chemo, 1 TKI and 1 platinum-based chemo, and 2 TKIs and no chemo. Repotrectinib RP2D was 160 mg once daily for 14 days, then 160 mg twice daily. Phase 2 primary endpoint was confirmed objective response rate (cORR) by Blinded Independent Central Review per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), intracranial ORR, cORR in TKI-pretreated pts with ROS1 G2032R NSCLC, and safety. Efficacy analyses included pts with ≥14 mo follow-up. Safety assessments included pts treated at RP2D across all study cohorts. Results: At data cutoff (December 19, 2022), median (range) follow-up in the primary efficacy cohorts was 24.0 (14.2–66.6) mo in the TKI-naïve cohort (n=71) and 21.5 (14.2–58.6) mo in the 1 prior TKI and no chemo cohort (n=56). In the TKI-naïve cohort, cORR was 79% (95% CI, 68–88). Median (95% CI) DOR was 34.1 (25.6–not estimable [NE]) mo; estimated 12- and 18-mo DOR rates were 83% (73–93) and 79% (68–90), respectively. Median PFS (95% CI) was 35.7 (27.4–NE) mo; estimated 12- and 18-mo PFS rates were 77% (66–87) and 70% (59–81), respectively. In the 1 prior TKI and no chemo cohort, cORR was 38% (95% CI, 25–52). Median DOR (95% CI) was 14.8 (7.6–NE) mo; estimated 12-mo DOR rate was 56% (34–77). Median PFS (95% CI) was 9.0 (6.8–19.6) mo; estimated 12-mo PFS rate was 41% (27–56). The median (range) time to response was 1.8 (0.9–5.6) mo in the TKI-naïve cohort and 1.8 (1.6–3.6) mo in the 1 prior TKI and no chemo cohort. Among pts with measurable brain metastasis at baseline, intracranial ORR was 89% (95% CI, 52–100) in the TKI-naïve cohort (n=9), and 38% (95% CI, 14–68) in the 1 prior TKI and no chemo cohort (n=13). In pts with TKI-pretreated ROS1 G2032R NSCLC (n=17), cORR was 59% (33–82). Among pts receiving repotrectinib at RP2D (n=426), treatment-emergent adverse events (TEAEs) occurred in 422 (99%), most commonly dizziness (62%). Grade ≥3 TEAEs occurred in 216 (51%) and were considered treatment-related in 122 (29%). TEAEs led to dose reduction and treatment discontinuation in 38% and 7% of pts, respectively. Additional analysis in CNS efficacy and by subsequent therapies will be presented. Conclusion: With a minimum follow-up of 14 mo in TRIDENT-1, repotrectinib continued to demonstrate durable efficacy in pts with ROS1+ NSCLC, including intracranial activity, in both TKI-naïve and 1 prior TKI and no chemo cohorts. Safety in pts treated at RP2D was manageable, consistent with previous reports in all treated pts. Prior:WCLC(Sep 10). Citation Format: Jessica J Lin, Byoung Chul Cho, D. Ross Camidge, Sang-We Kim, Benjamin Solomon, Rafal Dziadziuszko, Benjamin Besse, Koichi Goto, Adrianus Johannes de Langen, Jürgen Wolf, Ki Hyeong Lee, Sanjay Popat, Christoph Springfeld, Misako Nagasaka, Enriqueta Felip, Nong Yang, Shun Lu, Steven Kao, Vamsidhar Velcheti, Parneet Cheema, Shanna Stopatschinskaja, Minal Mehta, Denise Trone, Felipe Ades, Christophe Y. Calvet, Alexander Drilon. Repotrectinib in patients with ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC): Update from the pivotal phase 1/2 TRIDENT-1 trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR003.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».