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Ref Type

PMID

Authors

B.J. Solomon A. Drilon J.J. Lin L. Bazhenova K. Goto J. De Langen D-W. Kim J. Wolf C. Springfeld S. Popat D.W-T. Lim C.S. Baik A. Hervieu V. Moreno Garcia N. Yang S. Thamake F. Ades D. Trone B. Besse

Title

1372P Repotrectinib in patients (pts) with NTRK fusion-positive (NTRK+) advanced solid tumors, including NSCLC: Update from the phase I/II TRIDENT-1 trial

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Suppl 2	Oct 2023	S787-S788	Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(23)03242-8/fulltext

Abstract Text

Background Repotrectinib, a next-generation ROS1 and TRK tyrosine kinase inhibitor (TKI), has shown clinical activity and manageable safety in pts with ROS1+ NSCLC or NTRK+ locally advanced/metastatic solid tumors in the pivotal phase 1/2 TRIDENT-1 trial (NCT03093116). This is the first report of repotrectinib efficacy by Blinded Independent Central Review (BICR), with 8.7 mo minimum follow-up in pts with TKI-naïve and -pretreated NTRK+ solid tumors, including NSCLC, and safety in all pts treated at the recommended phase 2 dose (RP2D). Methods. Pts with NTRK+ solid tumors were enrolled in TKI-naïve and -pretreated cohorts. RP2D was 160 mg QD for 14 d, then 160 mg BID. Phase 2 primary endpoint: confirmed objective response rate (cORR) by BICR. Results At data cutoff (19 Dec 2022), median follow-up was 17.8 mo (range, 8.7–64.6) in the TKI-naïve cohort (n = 40), and 20.1 mo (8.7–69.4) in the TKI-pretreated cohort (n = 48). The table shows efficacy in pts with NTRK+ solid tumors and subgroups of interest. NSCLC was the most common tumor (TKI-naïve, 52%; TKI-pretreated, 29%). In TKI-naïve NTRK+ NSCLC, cORR was 62% (95% CI, 38–82) and estimated 12-mo duration of response (DOR) and progression-free survival (PFS) was 92% (95% CI, 76–100) and 64% (43–86), respectively. In TKI-pretreated NTRK+ NSCLC, cORR was 42% (18–71) and estimated 12-mo DOR and PFS was 44% (1–88) and 23% (0–49), respectively. In all pts treated at RP2D in TRIDENT-1 (n = 426), dizziness (62%; grade ≥3, 3%) was the most common treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs occurred in 51% of pts (29% treatment-related AEs). Treatment discontinuation rate due to TEAEs was 7% (3% due to treatment-related AEs). Conclusions In TRIDENT-1, with 8.7 mo minimum follow-up, repotrectinib showed robust responses and durable clinical activity in both TKI-naïve and -pretreated pts with NTRK+ solid tumors, including NSCLC. Repotrectinib safety at RP2D was manageable, consistent with prior reports.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
NTRK2 fusion	Advanced Solid Tumor	sensitive	Repotrectinib	FDA approved	Actionable	In a Phase I/II (TRIDENT-1) trial that supported FDA approval, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 58% (23/40), a 12-mo duration of response (DOR) of 86%, and 12-mo progression-free survival (PFS) of 56% in TKI-naive patients with advanced solid tumors harboring NTRK fusions, and a 50% (24/48) cORR, 39% 12-mo DOR, and 22% 12-mo PFS in TKI-pretreated patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116).	detail... detail...
NTRK1 fusion	Advanced Solid Tumor	sensitive	Repotrectinib	FDA approved	Actionable	In a Phase I/II (TRIDENT-1) trial that supported FDA approval, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 58% (23/40), a 12-mo duration of response (DOR) of 86%, and 12-mo progression-free survival (PFS) of 56% in TKI-naive patients with advanced solid tumors harboring NTRK fusions, and a 50% (24/48) cORR, 39% 12-mo DOR, and 22% 12-mo PFS in TKI-pretreated patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116).	detail... detail...
NTRK2 fusion	lung non-small cell carcinoma	sensitive	Repotrectinib	Phase Ib/II	Actionable	In a Phase I/II (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 62%, a 12-mo duration of response (DOR) of 92%, and 12-mo progression-free survival (PFS) of 64% in TKI-naive (n=21) patients with non-small cell lung cancer harboring NTRK fusions, and a 42% cORR, 44% 12-mo DOR, and 23% 12-mo PFS in TKI-pretreated (n=14) patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116).	detail...
NTRK1 fusion	lung non-small cell carcinoma	sensitive	Repotrectinib	Phase Ib/II	Actionable	In a Phase I/II (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 62%, a 12-mo duration of response (DOR) of 92%, and 12-mo progression-free survival (PFS) of 64% in TKI-naive (n=21) patients with non-small cell lung cancer harboring NTRK fusions, and a 42% cORR, 44% 12-mo DOR, and 23% 12-mo PFS in TKI-pretreated (n=14) patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116).	detail...