Abstract 144P
Background
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.
Methods
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.
Results
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: 144P
| Parameters | Results (n=8) |
| ECOG PS | |
| 0 | 6 (75) |
| 1 | 2 (25) |
| Adenocarcinoma | 8 (100) |
| Stage | |
| Ⅱ | 0 |
| ⅢA | 1 (12) |
| ⅢB | 5 (62) |
| ⅢC | 2 (25) |
| Driver variation | |
| ALK-fusion | 7 (88) |
| ROS1-fusion | 1 (12) |
| Radiation dose, Gy | 60.8 (range 60–66) |
| Interval between radiation and iruplinalkib, d | 24 (range 11–35) |
| CRT regimen | |
| Concurrent | 6 (75) |
| Sequential | 2 (25) |
| Chemotherapy regimen | |
| Cisplatin+pemetrexed | 3 (38) |
| Carboplatin+pemetrexed | 5 (62) |
| Iruplinalkib-related adverse event | 8 (100) |
| Grade ≥3 | 2 (25) |
| Leading to dose interruption/reduction/discontinuation | 2 (25)/1 (12)/0 |
| Best objective response | |
| Partial response | 2 (25) |
| Stable disease | 5 (62) |
| Progressive disease | 1 (12) |
| Objective response | 2 (25%, 95% CI 3%–65%) |
| Disease control | 7 (88%, 95% CI 47%–100%） |
Conclusions
Consolidative iruplinalkib after CRT showed acceptable safety and promising efficacy in ALK/ROS1+ unresectable NSCLC.
Clinical trial identification
NCT05351320.
Legal entity responsible for the study
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Funding
Qilu Pharmaceutical Co., Ltd., Jinan, China.
Disclosure
C. Zhu, Y. Sang, M. Wang, W. Xu: Financial Interests, Personal, Full or part-time Employment: Qilu Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.