KEY TAKEAWAYS
- The phase I/II trials aimed to evaluate outcomes of Phase 2 combination therapy in CPI-naive NSCLC patients.
- The primary efficacy endpoint was to determine ORR.
- The results showed well-tolerated and encouraging clinical activity, supporting its ongoing development in both low and high PD-L1 expression subgroups.
FLX475 (tivumecirnon), a selective CCR4 antagonist, aims to inhibit immunosuppressive regulatory T cells’ (Treg) recruitment to the tumor microenvironment (TME). In the FLX475-02 trial (NCT03674567), a phase 1/2 study, FLX475 is being investigated as monotherapy and in combination with pembrolizumab (pembro) in advanced cancer subjects. Early data have shown promising biologic effects, safety, and antitumor activity.
Tae Min Kim and his team aimed to present outcomes of the Phase 2 combination therapy cohort for subjects with non-small cell lung cancer (NSCLC) who have not received prior checkpoint inhibitor treatment (CPI-naive).
CPI-naive subjects with locally advanced or metastatic NSCLC were administered FLX475 100 mg orally once daily with pembrolizumab (200 mg IV Q3 weeks). The study aimed to assess safety, tolerability, and antitumor activity, with the primary endpoint being objective response rate (ORR) based on RECIST 1.1 criteria. Progression-free survival (PFS) was among additional efficacy endpoints. The data cutoff was August 31, 2023.
Among 35 evaluable subjects with relevant NSCLC histologies, median follow-up was 192 days (range: 9–660), and median prior therapy lines were 1 (range: 0–5). The only FLX475-related adverse event (AE) was reversible QT prolongation, managed by dose reduction. In all subjects (n=35), the confirmed partial response rate was 26%. In PD-L1-positive tumors (TPS ≥1%, n=20), the response rate was (ORR 35%), with 31% (5/16) and 50% (2/4) in low (TPS 1-49%) and high (TPS ≥50%) expression subgroups, respectively. As of the data cutoff, the PD-L1 TPS ≥1% subgroup showed a median PFS of 6.3 months, with 8 subjects still on treatment.
The results showed that FLX475 exhibited clear monotherapy efficacy and promising synergy with pembro and encouraging clinical activity, surpassing pembro monotherapy in PD-L1+ NSCLC. This was observed in both low (TPS 1-49%) and high (TPS ≥50%) PD-L1 expression groups, supporting the ongoing development of this combination therapy for NSCLC (based on historical results). Research is sponsored by RAPT Therapeutics, Inc.
Source: https://jitc.bmj.com/content/11/Suppl_2/1763
Clinical Trial: https://clinicaltrials.gov/study/NCT03674567
Kim TM, Ngamphaiboon N, Lee KH, et al. (2023) ‘’Phase 2 safety and efficacy of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with non-small cell lung cancer not previously treated with checkpoint inhibitor.’’ Presented at SITC 2023 ( 629-C).
