1494P - Fruquintinib combined with sintilimab and chemotherapy as the first-line treatment in advanced naive EGFR- and ALK-negative non-squamous non-small cell lung cancer(nsq-NSCLC): Updated results of a phase II trial

Background

Furoquitinib(F) is an orally highly selective tyrosine kinase inhibitor targeting VEGFR1,2,3. We previously reported some results of NCT04956146, which demonstrated that F plus PD-1 inhibitor sintilimab(S) and platinum-based chemotherapy(chemo) had encouraging efficacy and manageable toxicity as the first-line treatment for advanced naive EGFR- and ALK-negative nsq-NSCLC. Herein, we present updated results.

Methods

This single-arm, open-label, phase Ⅱ study consists of a safety lead-in phase (Part 1) and dose expansion phase (Part 2). In Part 1 the F taken orally at 5 mg (2 weeks on/ 1 weeks off, Q3W) plus S (200mg, iv, d1,Q3W) and chemo(Q3W). After 4∼6 cycles followed by maintenance therapy with F(RP2D) plus S and pemetrexed or not. DLT was observed for 1 cycle. The primary objective of Part 1 is to assess the safety and confirm the RP2D of F. The primary objective of Part 2 is to estimate the PFS and the secondary endpoints including ORR, DCR, OS, and safety.

Results

From February 2022 to May 2023, 26 pts were enrolled. The median age was 62 years, with males 92.3%, ECOG PS 0 73.1%, and the median sum of longest diameters (SLD) is 100.805mm. Pts with PD-L1 TPS ≥1%, ＜1%, and unknown were 14, 8, and 4 respectively. Of 20 evaluable pts, ORR and DCR were 80% and 100%. According to PD-L1 level, ORR was 91.7% and 57.1% for pts with PD-L1 TPS ≥1% and ＜1%. ORR was 60% for baseline SLD＜median SLD and 100% for median SLD＞median SLD. Median PFS was not reached yet. All pts experienced≥1 treatment-emergent adverse events (TEAEs). The most common Gr≥3 TEAEs (≥10% pts) were Neutrophil count decreased (42.3%), Anaemia(15.4%), Gamma-glutamyltransferase increased(11.5%) and hypertriglyceridaemia (11.5%).

Conclusions

This finding showed promising efficacy for fruquintinib combined with sintilimab and chemo in pts with advanced NSCLC as a first-line treatment with a manageable safety profile. This study might represent a potential treatment option for pts with unresectable or metastatic advanced naive EGFR- and ALK-negative nsq-NSCLC.

Clinical trial identification

NCT04956146; Release date: February 2, 2022.

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital with Nanjing Medical University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.