372O - Balstilimab (bal) alone or with zalifrelimab (zal) treatment for cervical cancer: An open-label, non-comparative, randomised, phase II trial

Background

Bal (anti-programmed death 1 [PD-1]) alone or combined with zal (anti-cytotoxic-T-lymphocyte-associated antigen 4 [CTLA-4]) has demonstrated durable clinical activity and favorable tolerability in Caucasian patients (pts) with locally advanced, unresectable or metastatic cervical cancer. Here, we reported the activity and safety of bal alone or plus zal in Chinese population.

Methods

In this open-label, non-comparative, randomised, phase II study, adult female pts had pathologically confirmed locally advanced, unresectable and/or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix with PD-L1 positivity, at least one measurable lesion by RECIST 1.1, an ECOG performance status of 0-1, and at least one previous line of systemic therapy. Pts were assigned (1:1) to intravenous bal 3 mg/kg q2w, or bal 3 mg/kg q2w + zal 1 mg/kg q6w over a 6-week cycle. A non-randomised expansion for bal monotherapy was added to further investigate efficacy. The primary endpoint was objective response rate (ORR) assessed by an independent review committee per RECIST 1.1.

Results

Between Oct 1, 2021 and Sep 15, 2022, 74 eligible pts received bal monotherapy, and 41 received bal + zal. 16/74 (21.6%) pts in the bal arm and 7/41 (17.1%) pts in the bal + zal arm received prior bevacizumab. The confirmed ORR was 25.7% (95% CI 16.2-37.2) in the bal arm and 36.6% (95% CI 22.1-53.1) in the bal + zal arm, with the median duration of response not reached in two arms. The median progression-free survival was 2.7 months (95% CI 1.6-4.2) and 5.7 (1.5-6.9), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) in bal arm were elevated AST (2.7%, 2/74) and anaemia (2.7%, 2/74); in bal + zal arm anaemia (7.3%, 3/41) and lymphopenia (4.9%, 2/41). Serious TRAEs were reported in 8 (10.8%) pts in the bal arm and 7 (17.1%) pts in the bal + zal arm. The pharmacokinetic (PK) profile of bal + zal was consistent with the data from bal monotherapy, indicating no impact of zal on the PK of bal.

Conclusions

Bal monotherapy and bal plus zal showed promising clinical efficacy and manageable safety profile in PD-L1 positive, recurrent or metastatic cervical cancer.

Clinical trial identification

NCT05033132.

Editorial acknowledgement

Legal entity responsible for the study

The licensed antibodies balstilimab and zalifrelimab were originally developed by Agenus Inc. These antibodies are partnered with Betta Pharmaceuticals Co. Ltd for certain P. R. China rights.

Funding

Betta Pharmaceuticals Co. Ltd.

Disclosure

P. Li, L. Ding: Financial Interests, Personal, Full or part-time Employment: Betta Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.