1329P - Fruquintinib combined with sintilimab and chemotherapy as the first-line treatment in advanced naïve EGFR- and ALK-negative non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results

Background

We have previously reported that fruquintinib (F) plus sintilimab (S) and platinum-based chemotherapy (chemo) as first-line therapy for advanced naïve EGFR- and ALK-negative nsq-NSCLC patients (pts) showed encouraging response and a favorable safety profile in this single-arm, phase II study (NCT04956146). Here, we aim to update some results.

Methods

This study consists of a safety lead-in phase (Part 1: F [5mg, po, d1-14, q3w] plus S [200mg, iv,d1,q3w] and chemo [q3w]) and dose expansion phase(Part 2). Maintenance therapy of F (RP2D) plus S with or without pemetrexed was performed after 4∼6 cycles. DLT was observed in the 1^st cycle. The primary objective of Part 1 was to assess safety and confirm RP2D of F. In part 2, the primary endpoint was PFS, the secondary endpoints were ORR, DCR, OS, and safety. In addition, subgroup analysis of ORR was performed.

Results

As of Feb 20, 2024, 38 pts (median age 64 [range: 47-79], 32 male, 29 ECOG PS 0, 10 brain metastasis, 28 MSS) were enrolled. Among them, pts with PD-L1 TPS ≥1% and ＜1% were 17 and 14 respectively. 26 pts (median SLD [sum of longest diameters] 93.5mm) were included in efficacy analysis, the median PFS was 11.33mo (95%CI: 9.69-NA) and 12mo-PFS rate was 47% with a median follow-up of 13.34 mo. The combination treatment provided an ORR of 80.77% (21 PR) and a DCR of 100% (5 SD). According to PD-L1 level, TPS ＜1% had higher ORR than TPS ≥1% (86.67% vs 70%). ORRs were 69.23% for baseline SLD＜median SLD and 92.31% for others. The ORR of brain metastasis pts was higher than that without brain metastasis (87.5% vs 77.78%). ORRs in TMB ≥10Mb and ＜10Mb were 100% and 70.59% respectively. ORR was 81.82% in MSS pts (18/22). All 26 pts showed evidence of a reduction in target tumor volume. Safety profile exhibited that the regimen was tolerable.

Conclusions

The updated results continued to support the clinical activity of fruquintinib combined with sintilimab and chemo as first-line therapy in unresectable or metastatic advanced naïve EGFR- and ALK-negative nsq-NSCLC pts with long-term follow-up, and the safety profile remained satisfactory. We will show more survival analysis data in the future.

Clinical trial identification

NCT04956146.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Province Hospital/The First Affiliated Hospital of Nanjing Medical University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.