874P - Preliminary outcomes from a phase Ib/II study of WX390 combined with toripalimab in patients with recurrent or metastatic head and neck squamous cell carcinoma

Background

Immune checkpoint inhibitors (ICIs) have become the standard of care for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most patients do not respond and effective options are lacking after failure of ICIs. WX390, a potent PI3K-mTOR dual inhibitor, has shown promise in preclinical studies. It modulates tumor environment and enhances anti-tumor immune responses by reducing Tregs and MDSCs.

Methods

We initiated a multicenter phase Ib/II study of WX390 and Toripalimab (anti-PD-1 antibody) across four cohorts: HNSCC, cervical cancer, urothelial carcinoma, and NSCLC. WX390 was administered orally at escalating doses of 0.7, 0.9, and 1.1 mg daily during phase Ib, with the RP2D established at 1.1 mg daily for the phase II expansion. Toripalimab was administered at 240 mg IV every three weeks. The primary endpoint for phase II was the overall response rate, assessed by RECIST 1.1. Here, we present the preliminary efficacy data for patients with HNSCC and the safety profile for all patients.

Results

As of Apr 25, 2024, a total of 65 patients were treated with WX390 combined with Toripalimab in Phase Ib/II trial. Among them 23 patients with R/M HNSCC were enrolled. Of these, 15 (65.2%) had received prior ICIs and 12 (52.2%) had undergone at least two previous lines. Objective response was achieved in 7 patients (ORR: 30.4%), including 2 (8.7%) complete responses and 5 (21.7%) partial responses. Disease control was observed in 15 patients (DCR: 65.2%). Among 65 patients, treatment-related adverse events (TRAEs) were observed in 60 patients (92.3%). The most common TRAEs included hyperglycemia (75.4%), weight loss (55.6%), and diarrhea (38.5%). Grade ≥3 TRAEs occurred in 43 patients (66.2%), with hyperglycemia (35.4%) and lymphocytopenia (13.8%) being the most frequently reported. Nine patients (13.8%) experienced TRAEs leading to a dose reduction of WX390. Three patients (4.6%) suffered TRAEs leading to the discontinuation of WX390. No grade 5 TRAEs were observed.

Conclusions

WX390 combined with Toripalimab demonstrated a manageable safety profile and encouraging antitumor effects in patients with R/M HNSCC. Further evaluations of this combination are ongoing.

Clinical trial identification

NCT06117566.

Editorial acknowledgement

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.