A TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced cervical cancers with prior anti-PD-(L)1 therapy.

5540 Background: Clinical findings on onatasertib (ATG-008), an oral TORC1/2 inhibitor, showed promising anti-tumor efficacy and manageable safety when used in combination with toripalimab, an anti-PD-1 monoclonal antibody, in treatment-naïve cervical cancer (CC) patients who had not received prior anti-PD-(L)1 therapy. Here, we present results from the anti-PD-(L)1 therapy treated CC cohort of the TORCH-2 study who had at least prior 1 line of anti-PD-(L)1 therapy 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. CC pts with at least prior 1 line of anti-PD-(L)1 therapy and 1 line of platinum chemotherapy regardless of PD-L1 expression, were enrolled and received onatasertib 15mg orally once a day (QD) in combination with tori 240 mg, once every 21 days (Q3W). Efficacy assessments were reported based on RECIST1.1 criteria and the endpoints included overall response rate (ORR), disease control rate (DCR), duration of response (DOR), progression free survival (PFS) and overall survival (OS). Results: As of Nov 25, 2024, 30 advanced CC pts who had at least prior 1 line of anti-PD-(L)1 therapy and 1 line of platinum chemotherapy were enrolled. Median age was 56.5 years. Baseline ECOG scores were 0 (26 pts) and 1 (4 pts). There were 14 and 16 pts who had received 1 and ≥2 prior lines of systemic therapy, respectively. Additionally, 16 pts had prior abraxane treatment and 11 pts had prior bevacizumab therapy. The median time since initial diagnosis was 37 months(m). The efficacy-evaluable population (27 CC pts) had an ORR of 22.2% (6/27, all confirmed). The DCR was 85.2%. The median time to response was 1.7 m (1.4, 4.2) and median DOR was 5.7 m (95% CI: 2.7, NE). Median PFS and median OS was 4.2 m (95% CI: 3.3, 5.8) and 21.4 m (95% CI: 15.5, NE), respectively. The ORRs of PD-L1 positive and PD-L1 negative populations were 30% (3/10) and 33.3% (2/6), respectively. Thirty pts (100%) had ≥ 1 TEAEs; 22 (73.3%) pts had grade ≥ 3 TRAEs. The most common all grade TRAEs included hyperglycaemia (56.7%), rash (43.3%) and white blood cell decreased (43.3 %). No TEAE led to death. Conclusions: Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in advanced CC pts with prior anti-PD-(L)1 therapy, regardless of PD-L1 expression. The expansion cohorts are ongoing. Clinical trial information: NCT04337463 .