On September 29, the ESMO 2019 Congress announced the results of the Phase Ib/II study evaluating Merck’s Keytruda in combination with Eisai’s lenvatinib for the treatment of advanced endometrial cancer. This open-label, single-arm Phase Ib/II KEYNOTE-146/Study 111 trial enrolled 108 patients with metastatic endometrial cancer who had experienced disease progression after at least one prior systemic therapy. Among these patients, 94 were non-MSI-H/dMMR, 11 were MSI-H/dMMR, and 3 had unknown tumor status. Patients received lenvatinib (20 mg once daily) plus Keytruda (200 mg once every 3 weeks), with a median follow-up duration of 18.7 months.
The results showed that among the 108 enrolled patients, regardless of their MSI-H/dMMR status, the ORR at Week 24 was 38.0% (n=41), meeting the primary endpoint. At the data cutoff, the overall ORR was 38.9% (n=42), with a complete response rate of 7.4% (n=8) and a partial response rate of 31.5% (n=34). The median DOR was 21.2 months.
Among 94 patients with non-MSI-H or dMMR endometrial cancer, the objective response rate (ORR) at week 24 with Keytruda in combination with Lenvatinib was 36.2%. At the data cutoff, the overall ORR was 37.2%, with a complete response rate of 7.4% and a partial response rate of 29.8%. The median duration of response (DOR) was not estimable. Regarding safety, adverse events leading to discontinuation occurred in 18.5% of patients.
Among 11 patients with MSI-H or dMMR tumors, the objective response rate (ORR) at week 24 with Keytruda plus Lenvatinib treatment was 63.6%. At the data cutoff, the overall ORR was 63.6%, with a complete response rate of 9.1% and a partial response rate of 54.5%. The median duration of response (DOR) was 21.2 months.
On September 18, 2019, the combination of Keytruda and Eisai’s Lenvatinib was just approved by the FDA for the treatment of specific advanced endometrial cancer, marking the first indication for this therapy to receive FDA approval. In August 2018, the FDA had granted it Breakthrough Therapy Designation; this was the second such designation for the therapy, with the first having been awarded in January 2018 for the treatment of renal cell carcinoma. Endometrial cancer is the most common type of uterine cancer, comprising a group of epithelial malignant tumors arising from the endometrium, and predominantly affecting perimenopausal and postmenopausal women. It is estimated that in 2018, there were over 380,000 new cases worldwide, and nearly 90,000 deaths from uterine cancer.