Efficacy And Safety Of Entrectinib In An Asian Population With Ntrk Fusion-Positive (Fp) Solid Tumours Or Ros1-Fp Nsclc

Entrectinib efficacy was established in an integrated analysis of 3 trials (ALKA-372-001 EudraCT 2012-000148-88; STARTRK-1 NCT02097810; STARTRK-2 NCT02568267) in adult pts with NTRK-fp tumours (objective response rate [ORR] 63.5%; data cutoff 31 Oct 2018) and ROS1-fp NSCLC (ORR 73.4%; data cutoff 1 May 2019). We conducted a subanalysis to confirm if entrectinib efficacy and safety in Asian patients is consistent with the total populations. Enrolled pts were NTRK and ROS1 TKI naïve with locally advanced/metastatic solid tumours or NSCLC, with/without baseline CNS metastases. Tumour response was assessed by blinded independent central review (BICR) using RECIST v1.1 after 4 wks and every 8 wks thereafter. Primary endpoints were ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The Asian efficacy-evaluable populations comprised 13 pts (17.6% of total population) with NTRK-fp tumours (breast, 1; colon, 2; NSCLC, 4; MASC, 4; sarcoma, 2) and 41 pts (43.6% of total population) with ROS1-fp NSCLC. Overall and intracranial efficacy outcomes are presented (Table). In pts with/without baseline CNS metastases (investigator assessed) overall ORR was 75.0% (3/4)/66.7% (6/9) for NTRK-fp tumours and 75.0% (15/20)/81.0% (17/21) for ROS1-fp NSCLC. In the Asian safety-evaluable populations, grade 1–2 and 3–4 treatment-related adverse events (TRAEs) were reported by 50.0% and 31.8% of pts with NTRK-fp tumours (n=22), and 57.1% and 33.0% of pts with ROS1-fp NSCLC (n=91). There were no grade 5 TRAEs. Discontinuations/dose reductions due to TRAEs occurred in 4.5%/27.3% of pts with NTRK-fp tumours and 6.6%/27.5% of pts with ROS1-fp NSCLC. Entrectinib treatment achieved high response rates with a manageable safety profile in Asian pts with NTRK-fp solid tumours or ROS1-fp NSCLC, with/without baseline CNS metastases, consistent with findings in the total populations.Table: 299MOEfficacy parameterNTRK-fp (N=13)ROS1-fp (N=41)Overall (n=13)Intracranial (n=3)*Overall (n=41)Intracranial (n=17)*ORR, n (%);95% CI9 (69.2);38.6–90.93 (100)32 (78.0);62.4–89.47 (41.2);18.4–67.1CR02 (66.6)5 (12.2)3 (17.6)PR9 (69.2)1 (33.3)27 (65.9)4 (23.5)SD002 (4.9)0PD1 (7.7)03 (7.3)4 (23.5)Non-CR/non-PD001 (2.4)4 (23.5)Missing/unevaluable3 (23.1)03 (7.3)2 (11.8)Median time to event, mos (95% CI)DoR in responders10.4 (5.7–NE)8.0−12.8†14.9 (9.1–NE)NE (4.6–NE)PFS14.9 (6.4–NE)8.9−13.8†13.6 (7.7–NE)5.4 (2.6–15.7)OSNE (14.9–NE)–NE (28.3–NE)–Median follow-up: NTRK-fp, 14.8 mos; ROS1-fp 19.8 mos *Baseline CNS metastases by BICR; †Range for 3 pts NE, not estimable Open table in a new tab