The LARA trial, conducted as a Phase II academic study in Singapore and South Korea, focused on recurrent clear cell gynecological cancer (CCGC) patients who had experienced progression after at least one prior platinum-based chemotherapy treatment and had not been exposed to immunotherapy previously. The trial employed a Simon 2-stage minimax design.

The primary endpoint of the study was to assess the objective response rate at the 24-week mark. Secondary endpoints included evaluating the CA125 response rate based on the Gynecologic Cancer InterGroup (GCIG) criteria, as well as examining progression-free survival (PFS), overall survival (OS), and the 24-week PFS rate.

From 26th March 2021  to 12th April 2023, 15 evaluable patients were enrolled to Stage I. The median duration of follow-up was 48.9 weeks. 4 out of 15 patients achieved confirmed objective response in the first 24 weeks (26.7%). Confirmed CA125 response (GCIG criteria) occurred in 9 out of 15 (60%) patients. The median PFS was 12 weeks and the PFS at 12 and 24 weeks were achieved in 46.7% and 33.3% of patients, respectively. As far as safety is concerned, all-grade toxicities occurred in 93.3% of patients Grade III toxicities occurred in 46.7% of patients.

Conclusion

Recurrent clear cell gynecologic cancers (CCGC) pose challenges with low response rates to chemotherapy or durvalumab monotherapy. To address this, a rational strategy involves combining anti-angiogenic and immune checkpoint blockade, supported by the unique gene expression profile and immune microenvironment in CCGC. Drawing inspiration from the success in clear cell renal cell carcinoma, where Anti-PD-1 + VEGF tyrosine kinase combinations have proven effective, the PD-1 inhibitor PL shows promise in reprogramming tumor-associated macrophages and enhancing cytotoxic T cell response.

Preliminary results from Stage I of the LARA trial reveal encouraging outcomes in pre-treated patients with advanced clear cell gynecological cancer. The trial has recently concluded its recruitment phase, and the comprehensive data will be presented at an upcoming meeting.

Reference reports by DelveInsight for more in-depth analysis and key coverage - 

• Clear Cell Ovarian Cancer Market Insight, Epidemiology, And Market Forecast
• Cervical Cancer Market Insight, Epidemiology, And Market Forecast
• Advanced Cervical Cancer Pipeline Insight
• Cervical Cancer Pipeline Insight