144P Preliminary safety and efficacy of iruplinalkib after chemoradiotherapy (CRT) in ALK/ROS1+ unresectable non-small cell lung cancer (NSCLC): Part 1 results from the INNOVATION study

Consolidative durvalumab after CRT is now the standard of care for unresectable NSCLC. The PACIFIC study showed a progression-free survival (PFS) of 8.4 months in patients with driver genes (including ALK+). Studies of consolidative targeted therapy after CRT for ALK/ROS1+ NSCLC were warranted. In Part 1 of the INNOVATION study, ALK/ROS1+ unresectable stage Ⅱ–Ⅲ NSCLC patients, who completed platinum-based concurrent or sequential CRT (54–66 Gy) were enrolled. Consolidative iruplinalkib (an anaplastic lymphoma kinase [ALK]/c-ros oncogene 1 [ROS1] inhibitor) was given orally at 180 mg/day (with a 7-day lead-in at 60 mg/day). The primary endpoint was grade ≥3 drug-related pneumonitis (DRP). Secondary endpoints included safety, overall response rate (ORR), disease control rate (DCR), PFS, etc. Between April 2022 and July 2023, a total of eight patients were enrolled in Part 1 of the study. Median age was 55 years (range 44–65). Three (38%) were male. Seven (88%) were non-smokers and one (12%) was a former smoker. Disease characteristics and treatment regimens are summarized in the table. As of the data cut-off on December 19, 2023, median follow-up for iruplinalkib treatment was 12.1 months. No DRP occurred. Six (75%) had radiation pneumonitis (grade 1–2) and were treated with corticosteroids. All these patients were recovering from radiation pneumonitis and continued iruplinalkib treatment at the previous dose. ORR and DCR for iruplinalkib were 25% (95% CI 3%–65%) and 88% (47%–100%), respectively. The tumors shrank in all patients after iruplinalkib treatment, except that one ROS1+ patient had a new lesion 4.5 months after iruplinalkib treatment initiation. PFS data were immature, with seven (88%) patients censored. Other endpoints were shown in the table. Table: 144PParametersResults (n=8)ECOG PS06 (75)12 (25)Adenocarcinoma8 (100)StageⅡ0ⅢA1 (12)ⅢB5 (62)ⅢC2 (25)Driver variationALK-fusion7 (88)ROS1-fusion1 (12)Radiation dose, Gy60.8 (range 60–66)Interval between radiation and iruplinalkib, d24 (range 11–35)CRT regimenConcurrent6 (75)Sequential2 (25)Chemotherapy regimenCisplatin+pemetrexed3 (38)Carboplatin+pemetrexed5 (62)Iruplinalkib-related adverse event8 (100)Grade ≥32 (25)Leading to dose interruption/reduction/discontinuation2 (25)/1 (12)/0Best objective responsePartial response2 (25)Stable disease5 (62)Progressive disease1 (12)Objective response2 (25%, 95% CI 3%–65%)Disease control7 (88%, 95% CI 47%–100%) Open table in a new tab Consolidative iruplinalkib after CRT showed acceptable safety and promising efficacy in ALK/ROS1+ unresectable NSCLC.