October 1, 2019

Impact: High

  • Merck and Eisai have announced that FDA has granted an accelerated approval to the combination treatment of Keytruda/Lenvima (pembrolizumab/lenvatinib) for patients with advanced endometrial carcinoma that is not MSI-H (microsatellite instability-high) or dMMR (mismatch repair deficient), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.
  • This accelerated approval is based on ORR and duration of response data from the Phase 2 KEYNOTE-146 trial (NCT02501096).
    • ORR = 38.3% (CR rate = 10.6%)
    • mDoR (median duration of response) = not reached (1.2+ to 33.1+ months)
    • % with duration of response ≥ 6 months = 69%
  • This accelerated approval was reviewed under FDA’s Real-Time Oncology Review (RTOR) pilot program (submission on June 17, 2019; accelerated approval on September 17, 2019).
  • Additionally, this review was conducted under Project Orbis. Project Orbis allows for a concurrent review process from multiple international regulatory agencies. For this approval, FDA, Australian Therapeutic Goods Administration (TGA) and Health Canada collaboratively reviewed the submission and made a simultaneous decision in all 3 countries.

inThought Analysis

As Keytruda continues to rack up approvals, what is most notable in this instance was the speed of the review process. Utilizing FDA’s RTOR program, this application was reviewed and approved in exactly 3 months. Further, the collaborative Project Orbis initiative permitted simultaneous approval in the U.S., Australia, and Canada, a regulatory milestone.

Keytruda/Lenvima had previously received Breakthrough Therapy Designation for this endometrial indication. The combination has also been granted Breakthrough status for HCC and RCC.

This mark’s the first PD-1 axis inhibitor approval specific to endometrial cancer. Previously, Keytruda was likely used for some cases of endometrial cancer via its site agnostic MSI-H label. It is estimated that ~25% of endometrial cancer patients are MSI-H.

In contrast to many other tumor types, endometrial cancer has seen relatively little PD-1 axis inhibitor development activity. In March, GSK announced positive Phase 1/2 results for its anti-PD-1, dostarlimab, and plans to file for a monotherapy 2L approval “at the end of 2019.” Also, Checkpoint Therapeutics has recently started enrolling patients into MSI-H and MSS endometrial cancer cohorts of a phase 1 trial of its anti-PD-L1 mAb, CK-301.

Sources: Merck Press Release

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