Multiple receptor tyrosine kinase inhibitor Lenvatinib ( Lenvima ) and anti–PD-1 therapy Pembrolizumab ( Keytruda ) as a combination therapy for patients with renal cell carcinoma received the designation based on results from the renal cell carcinoma cohort in Study 111.
The FDA ( Food and Drug Administration ) has granted Breakthrough Therapy Designation for Lenvatinib and Pembrolizumab as combination therapy for advanced and/or metastatic renal cell carcinoma ( RCC ).

Study 111, a multi-center, open-label phase 1b/2 clinical study in the United States and European Union, has evaluated the efficacy and safety of Lenvatinib in combination with Pembrolizumab in patients with selected solid tumors.

The primary objective of the phase 1b part of the study was to determine the maximum tolerated dose.
Patients with unresectable tumors ( renal cell carcinoma, endometrial cancer, non–small cell lung cancer, urothelial cancer, squamous cell head and neck cancer, and melanoma ) who had progressed after treatment with approved therapies or for which there are no current standard effectice therapies available were included in the study.
The participants were administered 24 mg of Lenvatinib orally daily in addition to 200 mg of Pembrolizumab intravenously every 3 weeks.

Phase 2 of the study was conducted with patients who had select solid tumors with 0 to 2 prior lines of systematic therapy with a recommended dosage of 20 mg of Lenvatinib daily in addition to 200 mg of Pembrolizumab every 3 weeks as determined based upon results of phase 1b.

The primary endpoint of phase 2 was objective response rate at 24 weeks after treatment was initiated, with select secondary endpoints including: objective response rate, disease control rate, progression-free survival, and duration of response.

The Breakthrough Therapy Designation is an FDA program that expedites the development and review of drugs for serious or life-threatening conditions. To qualify, there must be preliminary clinical evidence that demonstrates that the drug may provide substantial improvement over current available therapies or at least 1 clinically significant endpoint. ( Xagena )

Source: Merck, 2018