Despite advancements in the last two decades, there continues to be a high unmet need in patients with recurrent or metastatic cervical cancer, specifically due to its poor prognosis and limited treatment options.

Dual targeting of solid tumors with anti-PD-1 and anti--T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) monoclonal antibodies have been shown to enhance antitumor activity in recent preclinical and clinical studies. Hence, BeiGene is exploring the same concept by combining tislelizumab, a humanized IgG4 PD-1 inhibiting monoclonal antibody, and ociperlimab, a humanized Fc-intact IgG1 anti-TIGIT monoclonal antibody, as a novel treatment option for recurrent or metastatic cervical cancer.

AdvanTIG-202 is a randomized, multicenter, open-label Phase II trial evaluating the efficacy and safety of tislelizumab in combination with or without ociperlimab, in patients with recurrent or metastatic cervical cancer, who have received at least one line of prior chemotherapy.

The trial has two stages, where in Stage 1, patients were equally divided into two cohorts, where patients of Cohort 1 received 200 mg tislelizumab in combination with 900 mg ociperlimab every three weeks, while patients of Cohort 2 received 200 mg tislelizumab alone, until disease progression, unacceptable toxicity, or withdrawal of consent. In Stage 2, 98 additional patients were enrolled into Cohort 1, and were evaluated in the same way.

During ESMO 2023, only the primary analysis of Cohort 1 was presented. Based on the data cutoff date of 16 June 2022, 138 patients were enrolled and treated in Cohort 1, of which 84 had high PD-L1 expression. The median follow-up duration for all patients was 7.4 months.

The results were published in two groups, i.e. one group was all patients of Cohort 1, while the other was the 84 patients with high PD-L1 expression (PD-L1+). Below are the results in detail:

At the updated analysis of 1 June 2023, the median duration of response for Cohort 1 was 17.3 months, and for the PD-L1+ was 16.9 months. Additionally, with 12 month event free rates of 74.3% for Cohort 1 and 80% for PD-L1+, a durable response is indicated.

Patients of Cohort 2 that received tislelizumab only had an ORR of 32.5%, with 5 CRs and 8 PRs, suggesting the benefit of tislelizumab monotherapy in previously treated patients with recurrent or metastatic cervical cancer, but this cohort only had 40 patients, hence limiting the interpretability of its results due to its small sample size.

Looking at the safety profile of patients treated with tislelizumab in combination with ociperlimab, treatment-related adverse events (TRAEs) were observed in 67.4% of the patients, of which the most common were hypothyroidism (16.7%), pyrexia (11.6%), and rash (10.1%). Only 13% of the TRAEs were of Grade ≥3, while the occurrence of immune-related adverse events was observed in 21.7% of the patients. 

In the patients treated with tislelizumab monotherapy, TRAEs were observed in 60% of the patients, of which the most common was hypothyroidism (20%). Only 5% of the TRAEs were of Grade ≥3, while the occurrence of immune-related adverse events was observed in 22.5% of the patients. 

KOL insights

“The primary results AdvanTIG-202 shows how in the near future, tislelizumab in combination with ociperlimab could become a much needed new treatment option for patients with previously treated recurrent or metastatic cervical cancer, regardless of the PD-L1 expression of their tumors” - Medical Oncologist, Germany

Conclusion

The findings from the AdvanTIG-202 study solidified the potential of improved efficacy that can be achieved by the dual targeting of anti-PD-1 and anti-TIGIT in solid tumors, especially in cervical cancer. The antitumor activity and the durability of response showcases by the combination of tislelizumab with ociperlimab, shows their potentially superior efficacy in previously treated patients with recurrent or metastatic cervical cancer, regardless of PD-L1 expression of the tumors. Additionally, this combination treatment was also well tolerated in the studied population. This showcases how the tislelizumab + ociperlimab could become a new treatment option for cervical cancer patients in the near future.

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women worldwide. DelveInsight estimates that the total incident population of Cervical Cancer in the 7MM will reach over 45,000 by 2032. Estimates show that the highest incident population of Cervical Cancer is in the United States followed by Japan and Germany.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Cervical Cancer Market Insight And Market Forecast, Cervical Cancer Epidemiology Forecast and Cervical Cancer Pipeline Insight