A Phase 1/2 Study of the TORC1/2 Inhibitor Onatasertib Combined with Toripalimab in Patients with Advanced Solid Tumors: Cervical Cancer Cohort.

5509 Background: Preliminary clinical data of oral TORC1/2 inhibitor, onatasertib (ATG-008), demonstrated anti-tumor activity and acceptable tolerability when combined with toripalimab (tori), an anti-PD-1 monoclonal antibody in solid tumors, especially in cervical cancer (CC). Here, we present results from the anti-PD1 naïve CC cohort of the TORCH-2 study who had at least prior 1 line of chemotherapy with the combination of onatasertib and tori. Methods: The TORCH-2 study is a phase 1/2 open-label, dose escalation and expansion trial of Onatasertib in combination with tori in patients (pts) with advanced solid tumours (NCT04337463). Eligibility criteria included at least one measurable lesion, ECOG 0-1 and adequate organ function. Pts with prior PI3K/AKT/mTOR inhibitor therapy were excluded, regardless of PD-L1 expression. Onatasertib was administered 15mg orally once a day (QD) in combination with tori 240 mg, once every 21 days (Q3W), which is the recommended phase 2 dose for the combination based on previous data. Efficacy assessments were reported based on RECIST1.1 criteria. Results: As of Oct 20, 2023, 31 checkpoint inhibitor (CPI) naïve advanced CC pts who had at least prior 1 line of systemic chemotherapy were enrolled. Median age was 54 years. Baseline ECOG scores were 0 (11 pts) and 1 (20 pts); 29 pts had stage IV disease. There were 19 and 12 pts who had received 1 and ≥2 prior lines of systemic therapy, respectively. The median time from last prior systemic therapy was 16.7 months(m). The efficacy-evaluable population (30 CC pts) had an overall response rate (ORR; best response) of 53.3% (16/30, 3 responders unconfirmed), including 4 CR and 12 PR. The disease control rate was 86.7%. The median time to response was 1.4 months. Median progression free survival (PFS) and 24m PFS rate was 8.4 m and 31.0%, respectively. Median overall survival (OS) was not reach and 24m OS rate was 51.6%. The ORRs of PD-L1 positive, PD-L1 negative, and PD-L1 NA populations were 61.5% (8/13), 55.6% (5/9), and 37.5% (3/8), respectively. One CC pt with negative PD-L1 expression achieved CR and remains on treatment for over 3 years. Thirty pts (96.8%) had ≥ 1 TEAEs; 13 (41.9%) pts had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs included rash (12.9%), lymphocyte count decreased (9.7 %), and decreased platelet count (6.5%). Conclusions: Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in CC pts at the RP2D combination dose, regardless of PD-L1 expression. Enrolment in the expansion cohort for CPI-treated CC is ongoing, and updated data will be presented. Clinical trial information: NCT04337463 .