Lenvatinib (Lenvima) plus pembrolizumab (Keytruda) demonstrated evidence of tumor responses in patients with stage III/IV or recurrent endometrial carcinoma regardless of mismatch repair–proficient (pMMR) status, histology, and prior adjuvant therapy, according to findings from an exploratory analysis of the phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) presented at the 

Topline results from the study reveal that as of the data cut-off date of October 2, 2023, 55.7% of patients treated with the lenvatinib combination achieved an objective response, including 50.6% of the pMMR population. Furthermore, the median duration of response (DOR) was 16.1 months (range, 1.0+-48.7+) and 23.2 months (1.0+-49.0+), for all-comers and the pMMR population, respectively.

“Clinically meaningful response rates were seen regardless of baseline characteristics including MMR status, histology, and prior adjuvant therapy,” Anna Dańska-Bidzińska, MD, a gynecologist from Warsaw Medical University in Warsaw, Poland, wrote in the presentation with study coinvestigators. “Patients who experienced a response to lenvatinib plus pembrolizumab, especially patients demonstrating a [complete response (CR)], had promising [progression-free survival (PFS)] and [overall survival (OS)].”

Additional data show a median time to objective response of 2.1 months (range, 1.3-26.4) and 2.1 months (1.2-26.4) among all-comers and pMMR patients, respectively. In each respective group, the median duration of treatment exposure for responders was 17.1 months (range, 1.5-48.4) and 19.8 months (1.5-51.5).

Furthermore, Kaplan-Meier PFS estimates by response in the pMMR population was 18.4 months (95% CI, 15.1-26.8) among all responders and 13.9 months (95% CI, 12.3-15.6) among patients with a partial response (PR), and for those with a CR it was not reached ([NR]; 95% CI, 29.1-NR). Among all-comers, it was 27.3 months (95% CI, 20.9-36.8), 15.1 months (95% CI, 12.9-19.4), and NR (95% CI, NR-NR) respectively.

Kaplan-Meier OS estimates by response in the pMMR population was 43.6 months (95% CI, 37.9- NR) among all responders, 37.6 months (95% CI, 30.9-NR) among patients with a PR, and NR (95% CI, 39.5-NR) for those with a CR. Among all-comers, it was NR (95% CI, 47.0-NR), 43.5 months (95% CI, 32.7-NR), and NR (95% CI, NR-NR), respectively.

The phase 3, multicenter, open-label study randomly assigned patients 1:1 with stage III to IV recurrent endometrial carcinoma to receive lenvatinib at 20 mg orally daily until disease progression plus pembrolizumab at 200 mg intravenously every 3 weeks until disease progression or 35 cycles. In the comparator arm, patients received paclitaxel at 175 mg/m

 intravenously plus carboplatin at area under the curve 6 intravenoulsy every 3 weeks for up to 7 cycles.

The study’s dual primary end points were PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. Secondary end points included objective response rate (ORR) per RECIST v1.1 by BICR, safety, and health-related quality of life. Exploratory end points included DOR per RECIST v1.1 by BICR.

Among responders in the lenvatinib combination group, all experienced adverse events (AEs). Any-grade and grade 3 or higher treatment-related AE (TRAE) occurrence was 99.1% and 82.5%, respectively. Discontinuation of lenvatinib, pembrolizumab, or both due to TRAEs occurred in 27.8%, 18.8%, and 3.4% of patients, respectively. Notably, a single treatment-related grade 5 instance of pneumonitis occurred.

“This exploratory analysis from the ENGOT-en9/LEAP-001 study provides evidence of substantial antitumor activity with lenvatinib plus pembrolizumab,” Dańska-Bidzińska and study coinvestigators concluded in the presentation. “Responses among patients in the lenvatinib plus pembrolizumab arm were both deep and durable…AEs among patients who experienced a CR or PR were manageable with dose modifications and supportive care.”

Dańska-Bidzińska A, Makker V, Salutari V, et al. Characterization of tumor responses with lenvatinib plus pembrolizumab in the ENGOT-en9/LEAP-001 study. Presented at the European Society for Medical Oncology (ESMO) Congress 2024. September 13-17, 2024; Barcelona, Spain. Abstract 737P.

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