724P - Preliminary outcomes from a phase Ib/II study of the highly potent PI3K-mTOR dual inhibitor WX390 combined with toripalimab in patients with advanced cervical cancer

Background

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of recurrent or metastatic cervical cancer. However, patients rarely respond to ICIs treatments, and there are no effective options after ICIs failure. WX390 is a potent dual inhibitor of PI3K and mTOR. It has been shown to enhance the immune responses by reducing Tregs and MDSCs in preclinical models. We initiated a multicenter phase 1b/2 study of WX390 in combination with Toripalimab (anti-PD-1 antibody) across four cohorts: HNSCC, cervical cancer, urothelial carcinoma, and NSCLC. Here, we present the preliminary data for patients with cervical cancer.

Methods

Patients were administrated with WX390 at doses of 0.7, 0.9, or 1.1 mg QD orally for dose escalation (phase 1b) and at a dose of 1.1 mg QD (RP2D) for dose expansion (phase 2), along with Toripalimab 240 mg IV every 3 weeks. The phase 2 was designed to evaluate the preliminary efficacy. Analyses were conducted on cervical cancer patients who were required to have at least one lesion measurable by RECIST v1.1, and the disease must have relapsed after a prior-line, platinum-based regimen.

Results

As of April 25, 2024, a total of 24 patients with cervical cancer were enrolled. All patients had a history of radiotherapy, and 11 (45.8%) had received prior ICIs. Among the 18 patients evaluable for efficacy, the objective response rate (ORR) was 44.4% (8/18), and the disease control rate (DCR) was 83.3% (15/18). Partial response was observed in 55.6% (5/9) of ICI-naïve patients, and 33.3% (3/9) in ICI-pretreated patients. Treatment-related adverse events (TRAEs) were reported in 20 (83.3%) patients. The most common TRAEs included hyperglycemia (70.8%), diarrhea (45.8%), and hypophosphatemia (45.8%). The most common grade ≥3 TRAEs were hyperglycemia (45.8%) and diarrhea (16.7%). TRAE leading to dose reduction occurred in 1 (4.2%) patient. No TRAE leading to dose discontinuation or death was reported.

Conclusions

WX390 combined with Toripalimab demonstrated a manageable safety profile and promising antitumor effects in patients with advanced cervical cancer. Further assessments of antitumor response and safety are currently ongoing in a larger cohort of patients.

Clinical trial identification

NCT06117566.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.