The effectiveness of immunotherapy in first-line treatment of recurrent or metastatic cervical cancer was proved by the recent approval of the combination of pembrolizumab and chemotherapy, with or without bevacizumab, in patients whose tumors expressed PD-L1 (PD-L1 Combined Positive Score ≥1).

Currently, the preferred standard first-line treatment for recurrent or metastatic Cervical Cancer is cisplatin or carboplatin and paclitaxel plus bevacizumab, but in patients with positive PD-L1 expression, the PD-1 inhibitor pembrolizumab in combination with chemotherapy, with or without bevacizumab, is recommended. While this recent inclusion of PD-1 inhibitor with the standard or care has significantly improved patient survival, the survival benefits for patients remain limite
Qilu Pharma’s bi-specific PD-1/CTLA-4 blocker, QL1706 shows promise in the first-line treatment of recurrent or metastatic cervical cancerd, indicating an unmet clinical need.

QL1706 is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies iparomlimab and tuvonralimab (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life for CTLA-4.

This multicentered, open-label Phase II trial evaluated the efficacy and safety of QL1706 in combination with paclitaxel and platinum-based chemotherapy, with or without bevacizumab, in 60 patients with recurrent or metastatic cervical cancer, who have not received prior systemic therapy. The patients were equally divided into two cohorts, where patients of Cohort 1 received QL1706 in combination with either cisplatin or carboplatin and paclitaxel, while patients of Cohort 2 received the same regimen as Cohort 1, but with the addition of bevacizumab.

With a median follow-up of 14 months, in the 58 patients who received at least one post-baseline efficacy evaluation, objective response rate was 81%, where eight patients achieved a complete response while 39 achieved a partial response. The disease control rate was 98.3%, with a median progression free survival (PFS) of 14.3 months.

Although the median Overall Survival (OS) has not yet been reached, the patients of Cohort 2, that received bevacizumab ontop of the combination of QL1706 and chemotherapy, had a median PFS of 16.4 months.

Regarding the safety profile of QL1706, treatment-related adverse events (TRAEs) were observed in all patients, with the most common ones being white blood cell count decrease (71.3%), neutrophil count decrease (68.3%), and anemia (43.3%). Treatment-related serious adverse events occurred in 33.3% of the patients, with the occurrence of immune-related adverse events being 13.3%. 26.7% of the patients had to discontinue treatment due to treatment-related adverse events and the incidence of treatment-related death was 1.7%, which was possibly related to bevacizumab.

KOL insights

“The results from this Phase II trial of QL1706 not only establishes its future prospect of improving the first-line treatment of recurrent or metastatic cervical cancer patients in patients with low PD-L1 expression, but also proves its potential in improving the treatment outcomes of patients with PD-L1 expression” - Associate professor, Medical Gynecological Oncology, USA

Conclusion

QL1706 in combo with chemotherapy ± bevacizumab showed promising efficacy and antitumor activity, along with a tolerable safety profile, in the first-line treatment of patients with recurrent or metastatic cervical cancer. The results from this Phase II trial further solidifies the basis of the Phase III trial of the same regimen in the same patient population, to further establish the statistical significance of its outcomes along with their clinical meaningfulness.

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 and Cervical Cancer Epidemiology Forecast