2166 - Chemoradiotherapy (CRT) Combined with Consolidative Iruplinalkib for ALK/ROS1+ Unresectable Non-Small Cell Lung Cancer (NSCLC): ALK+ Cohort Results from Part 1 of the INNOVATION Study

L. Wang¹, B. Zou¹, H. Zhou², X. Zhang¹, X. Meng¹, H. Zhu¹, M. Gao³, C. Zhu⁴, Y. Sang⁴, M. Wang⁴, and J. Yu¹; ¹Shandong Cancer Hospital and Institute, Jinan, China, ²Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ³Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ⁴Qilu Pharmaceutical Co., Ltd., Jinan, China

Purpose/Objective(s): The standard of care for unresectable NSCLC is consolidative durvalumab plus CRT. However, in clinical practice for ALK+ unresectable disease, anaplastic lymphoma kinase (ALK) inhibitors were commonly used but without the evidence of CRT + ALK inhibitor. The INNOVATION study aimed to evaluate the safety and efficacy of CRT + iruplinalkib for patients with ALK/ROS1+ unresectable NSCLC. Materials/

Methods: In Part 1 of the INNOVATION study, ALK/ROS1+ unresectable stage ?–? NSCLC patients with ECOG performance status (PS) of 0–1, who completed platinum-based concurrent or sequential CRT (54–66 Gy) were eligible. Patients received oral iruplinalkib 180 mg/day, with a 7-day lead-in at 60 mg/day. The primary endpoint was grade =3 drug-related pneumonitis (DRP) within 90 days after radiation therapy completion.
Results: From April 2022 to July 2023, 8 patients were enrolled in Part 1. Among 7 ALK+ patients, median age was 54 years (range 44–65), and 3 patients (43%) were male. Most of the patients (6 cases, 86%) were non-smokers and 5 cases (71%) had ECOG PS of 0. Tumor characteristics and CRT regimens were shown in the Table. As of the data cut-off on December 19, 2023, median follow-up for CRT + iruplinalkib was 17.7 months. No grade =3 DRP was observed, which met the primary endpoint. 4 and 3 of 7 patients had grade 1 and 2 pneumonitis, respectively. No dose reduction or discontinuation of iruplinalkib due to pneumonitis was reported. Grade 3–4 iruplinalkib-related adverse events occurred in two (29%) patients (1 case of blood creatine phosphokinase increased and 1 case of hypercholesterolaemia). From the start of CRT, overall response rate was 86% (95% CI 42%–100%), and disease control rate was 100% (59%–100%). Progression-free survival (PFS)/time to progression (TTP) data were immature, with no event occurred. 12-month PFS/TTP rate was 100%. Other endpoints were shown in the Table.
Conclusion: CRT + consolidative iruplinalkib was well-tolerated and had encouraging efficacy in ALK+ unresectable NSCLC. This innovative regimen may be an ideal option for this population. Abstract 2166 – Table 1

Parameters	Results (n=7)
Adenocarcinoma	7 (100)
Stage
?	0
?A	1 (14)
?B	4 (57)
?C	2 (29)
Median radiation dose, Gy	60 (range 60–66)
Median interval between radiation and iruplinalkib, d	23 (range 11–35)
CRT regimen
Concurrent	5 (71)
Sequential	2 (29)
Chemotherapy regimen
Cisplatin+pemetrexed	3 (43)
Carboplatin+pemetrexed	4 (57)
Iruplinalkib-related dose interruption/reduction/discontinuation	2 (29)/1 (14)/0
From the start of CRT
Best objective response
Partial response	6 (86)
Stable disease	1 (14)
Progressive disease	0
Objective response	6 (86%, 95% CI 42%–100%)
Disease control	7 (100%, 95% CI 59%–100%)
From the start of iruplinalkib treatment after CRT
Objective response	2 (29%, 95% CI 4%–71%)
Disease control	7 (100%, 95% CI 59%–100%)