The phase Ib/II Study 111 examining the combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) in women with metastatic endometrial carcinoma has been expanded based on positive interim results, according to Eisai, the manufacturer of lenvatinib.
Eisai, which is partnering with Merck, the developer of the PD-1 inhibitor pembrolizumab, reported today that researchers hope to expand enrollment from the current 23 patients to approximately 100 women.
In findings from Study 111 reported at the 2017 ASCO Annual Meeting, 24-week follow-up data showed that the combination of lenvatinib and pembrolizumab induced an objective response rate (ORR) of 52.2% (95% CI, 30.6-73.2) based on independent radiologic review and 47.8% (95% CI, 26.8-69.4) based on investigator review. The median duration of response was not yet evaluable.
In Study 111, 23 patients were assigned to 20 mg of oral lenvatinib daily plus 200 mg of pembrolizumab IV every 3 weeks on a 21-day treatment cycle. All patients had an ECOG performance score of 0 or 1. Eligible patients could not have received anticancer treatment within 28 days of enrollment and could not have had prior treatment with lenvatinib or any anti–PD-1, anti–PD-L1, or anti–PD-L2 therapy.
Median age was 64 and 87% of the cohort was white. All patients had undergone at least 1 prior treatment. Most (60.9%) had undergone 2 prior treatments. Eleven patients remained on-study at the time of the analysis.
Median progression-free survival (PFS) was 9.7 months (95% CI, 4.2-not evaluable) according to investigator review. PFS could not be evaluated by independent radiological review.
No patient achieved a complete response, but 11 patients each had partial response (47.8%) or stable disease (47.8%). The disease control rate at ≥5 weeks was 95.7% (95% CI, 78.1-99.9) by investigator review and 91.3% (95% CI, 72.0%-98.9%) by independent radiological review.
The clinical benefit rate was 73.9% (95% CI, 51.6-89.8) by investigator review and 65.2% (95% CI, 42.7-83.6) by independent radiological review.
One patient was microsatellite instability-high (MSI-H), 13 were non–MSI-H, 8 patients were not tested, and the MSI status of 1 patient was unknown. Investigators said that the study combination was associated with tumor shrinkage regardless of MSI status.
All patients experienced treatment-emergent adverse events (TEAEs), though most were mild. Researchers reported that toxicities were manageable with dose modifications, interruptions, and discontinuations. Moreover, the AEs associated with the combination were similar to those observed with each drug as a monotherapy.
Only 1 patient experienced a grade 4 TEAE—a single incident of hypertension.
Overall, 19 patients experienced grade 3 TEAEs. Researchers observed 7 cases (30.4%) of hypertension, 2 cases (8.7%) each of fatigue and Palmar-plantar erythrodysesthesia syndrome, and 1 case each of diarrhea, nausea, proteinuria, rash maculopapular, and urinary tract infection.
The most common all-grade TEAEs included fatigue (n = 15; 65.2%), hypertension (n = 15; 65.2%), diarrhea (n = 13; 56.5%), nausea (n = 12; 52.2%), and arthralgia (n = 11; 47.8%).
Endometrial carcinoma is the sixth most common cancer in women worldwide, with 320,000 new cases diagnosed in 2012. In the United States, it is estimated that there will be 60,000 new cases and 10,000 deaths attributed to the disease in 2017. There currently is no drug approved for second-line therapy.
Makker V, Rasco DW, Dutcus CE, et al. A phase Ib/II trial of lenvatinib (LEN) plus pembrolizumab (Pembro) in patients (Pts) with endometrial carcinoma. J Clin Oncol. 2017;35 (suppl; abstr 5598).