The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Treatment with lenvatinib plus pembrolizumab resulted in antitumor efficacy among patients with metastatic renal cell carcinoma (RCC) that had progressed with previous immune checkpoint inhibitor (ICI) therapy, according to results from the phase 2 Study 111/KEYNOTE-146 trial presented at the ASCO20 Virtual Scientific Program.

“The combination of TKIs [tyrosine kinase inhibitors] and ICIs has become a new standard of care in the first-line treatment of RCC,” said Chung-Han Lee, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, and lead author and presenter of the study.

Data from the phase 1b portion of the Study 111/KEYNOTE-146 trial was previously reported, and showed initial efficacy. Dr Lee presented data from the phase 2 cohort.  

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The open-label phase 2 cohort of Study 111/KEYNOTE-146 trial treated 104 patients with metastatic clear cell RCC that had progressed during or after ICI treatment with lenvatinib plus pembrolizumab. The primary endpoint was objective response rate (ORR) at 24 weeks as measured by irRESIST criteria. Secondary endpoints included ORR, progression-free survival (PFS), overall survival (OS), and safety.

At baseline, median age of patients was 60 and 77% were male. Prior nephrectomy had been performed in 75% of patients. The Memorial Sloan Kettering Cancer Center risk group was favorable in 36%, intermediate in 42%, and poor in 22% of patients. PD-L1 expression was present in 42% of patients. All patients had measurable disease by irRESIST and 62% had received 2 or more prior therapies.

The ORR at week 24 was 51% (95% CI, 41%-61%); the overall ORR was similar at 55%. The duration of response was 12 months.

The median PFS was 11.7 months (95% CI, 9.4-17.7 months), with a 1-year PFS of 44%. The median OS was not yet reached, with a 1-year rate of 77%.

In a subgroup analysis, the ORR was similar regardless of prior ICI-based treatment. “Tumor shrinkage and objective responses could be observed regardless of whether patients received prior VEGF targeted therapy,” Dr Lee said.

The most common treatment-related adverse events (TRAEs) included fatigue, proteinuria, hypertension, dysphonia, arthralgia, and gastrointestinal effects. Two grade 5 TRAEs occurred due to upper gastrointestinal hemorrhage or sudden death.

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TRAEs resulted in 43% of patients receiving a dose reduction of lenvatinib during the first 4 cycles, and another 26% after the fourth cycle. Treatment discontinuation of either lenvatinib or pembrolizumab occurred in 12% of patients due to TRAEs.

“In conclusion, lenvatinib plus pembrolizumab demonstrated promising antitumor activity in patients with metastatic clear-cell RCC who had previously progressed on prior PD-1/PD-L1 therapy,” Dr Lee said. A phase 3 study is ongoing.

Research funding for this study was provided by Eisai Inc and Merck Sharp & Dohme Corp.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Lee CH, Shah AY, Hsieh JJ, et al. Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 5008.