Digital representation of cervical cancer
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Cervical cancer is the most common gynecological cancer and is the fourth leading cause of cancer death among women worldwide. Despite advances in the understanding of the diseases and the development of new treatments, therapeutic approaches for women with recurrent or metastatic disease remain suboptimal.

Yet results released in late December by biotech company Agenus from a global Phase II clinical study of PD1 inhibitor balstilimab (Bal) and plus anti-CTLA4 monoclonal antibody zalifrelimab (Zal) show promise as a second-line treatment for recurrent/metastatic cervical cancer patients who had relapsed after treatment with platinum-based therapy.

Data from the 125 evaluable patients treated with Bal/Zal combination showed an objective response rate (ORR) of 32.8% in PD-L1-positive patients and 25.6% in all patients regardless of PD-L1 status. This response rates and the durability of response are higher than those demonstrated in approved therapies for these patients, while median duration of response had not yet been reached at follow-up at a median of 21 months.

Currently, the only approved immunotherapy for use in this clinical setting is pembrolizumab, an anti-PD1 antibody which received accelerated approval for the treatment of patients with programmed death ligand-1 (PD-L1)–positive recurrent and/or metastatic cervical cancer after disease progression on or after chemotherapy. This approval and the success of pembrolizumab proved that the approach of targeting the PD-1 and PD-L1 immune checkpoint axis as a therapeutic approach in this malignancy was viable.

Regarding the Bal/Zal combination therapy study, according to Steven O’Day, M.D., CMO of Agenus. “The combination data with Bal (anti-PD-1) and Zal (anti-CTLA-4) in recurrent/metastatic cervical cancer represents a meaningful improvement over currently available therapies while demonstrating a well-tolerated safety profile. We are committed to pursuing the benefit of combination therapies with first-generation antibodies like Zal as well as with our next-generation candidates which include our Fc-enhanced anti-CTLA-4 antibody AGEN1181.”

In total, 155 women (median age, 50 years and rangin in age from 24 to 76 years) were treated with balstilimab plus zalifrelimab. Of those patients, 125 had measurable disease at baseline and one prior line of platinum-based therapy in the advanced setting, and these patients constituted the efficacy-evaluable population. The confirmed ORR was 25.6% (95% CI, 18.8 to 33.9), including 10 complete responders and 22 partial responders, with median duration of response not reached (86.5%, 75.5%, and 64.2% at 6, 9, and 12 months, respectively). The ORRs were 32.8% and 9.1% in patients with programmed death ligand-1–positive and programmed death ligand-1–negative tumors, respectively. For patients with squamous cell carcinoma, the ORR was 32.6%. The overall disease control rate was 52% (95% CI, 43.3 to 60.6). Hypothyroidism (14.2%) and hyperthyroidism (7.1%) were the most common immune-mediated adverse events.

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