767P - Phase I/II study of toripalimab with cisplatin-based concurrent IMRT for local advanced cervical cancer

Background

Cisplatin-based concurrent chemoradiation therapy (CCRT) has been increasingly used for local advanced cervical cancer (LACC). However, recurrence is common after cisplatin-based CCRT. Several treatment strategies have been explored to further improve the outcome. We aimed to evaluate the safety and efficacy of anti-PD-1 (Toripalimab, a humanized immunoglobulin G monoclonal antibody against programmed death 1) combined with cisplatin-based concurrent IMRT for locally advanced cervical cancer.

Methods

This is an open-label, nonrandomized, prospective phase Ⅰ/II study in a single arm. Patients with untreated LACC (2018 FIGO stage IB3, IIA –IVA) were enrolled. All patients were treated with CCRT for 56 days including cisplatin (40 mg/m2, Q1W) combined with image-guidance volume modulated Arc therapy (IG-VMAT) to pelvis (50.4Gy in 28 fractions, pelvic and paraortic nodes with simultaneous nodal boost to 59.4 Gy, 28 fractions), and followed by HDR intracavitary (30-36 Gy in 5-6 fractions) brachytherapy. Toripalimab was administered intravenously at 240 mg every 2 week for 4 cycles. The primary endpoint was incidence and severity of acute adverse events up to 3 months of completing treatment. The secondary endpoints were ORR and PFS.

Results

From Sep 2020 to Sep 2022, a total of 30 patients were enrolled. Median age was 58 years [range: 23–71]. The median follow-up duration was 8.5 months [range: 3.2–27.3]. 29 patients (29/30, 96.7%) completed the treatment, 1 patient (1/30, 3.3%) terminated the treatment because of hemophagic syndrome, who with a history of liver fluke disease. ORR was 100.0% (30/30) at 3 months after treatment. Treatment-related grade 3 or 4 adverse events occurred in 80% (24/30) of patients, primarily leukopenia (63.3%), lymphopenia (36.7%), anemia (26.7%), neutropenia (16.7%). The grade 1-2 potentially immune-related adverse events were chromatosis 5 (16.7%), rash 2 (6.7%), pruritus 2 (6.7%), hypothyroidism 2 (6.7%), adrenal insufficiency 2 (6.7%), No treatment-related deaths occurred.

Conclusions

Toripalimab combined with cisplatin-based concurrent IMRT was tolerable and showed promising antitumor activity in patients with LACC, while immunotherapy-related toxicities should be carefully managed.

Clinical trial identification

NCT04368273.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Shanghai Junshi Biomedicine Technology Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.