Merck and Eisai's Phase 3 LEAP-015 trial evaluating Keytruda (pembrolizumab) plus Lenvima (lenvatinib) in combination with chemotherapy for first-line treatment of locally advanced unresectable or metastatic HER2-negative gastroesophageal adenocarcinoma showed mixed results. While the combination demonstrated a statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR), it failed to meet its other primary endpoint of overall survival (OS) at the final analysis. The full data will be presented at an upcoming medical meeting.
LEAP-015 Trial Details
The LEAP-015 trial was a randomized, open-label, Phase 3 study comparing Keytruda plus Lenvima with chemotherapy versus chemotherapy alone. The dual primary endpoints were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review (BICR). Key secondary endpoints included objective response rate (ORR) and duration of response (DOR), also assessed by BICR, and safety.
In the trial, up to 880 patients were randomized 1:1 to receive:
- Keytruda plus Lenvima plus chemotherapy:
- Induction Phase (approximately 12 weeks): Keytruda 400 mg intravenously (IV) every six weeks (Q6W) x 2 cycles plus oral Lenvima 8 mg every day (QD) plus chemotherapy (CAPOX or mFOLFOX6).
- Consolidation Phase: Keytruda 400 mg IV Q6W (up to 16 doses) plus oral Lenvima 20 mg QD; or Chemotherapy (either CAPOX regimen or mFOLFOX6 regimen).
Keytruda and Lenvima
Keytruda is an anti-PD-1 therapy that increases the ability of the body’s immune system to detect and fight tumor cells. Lenvima is an orally available multiple receptor tyrosine kinase inhibitor (TKI) that inhibits the kinase activities of VEGF receptors and other kinases involved in angiogenesis, tumor growth, and cancer progression.
Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma is a challenging disease to treat and a leading cause of cancer death worldwide. Gastric cancer tends to develop slowly over many years and rarely causes early symptoms, resulting in most cases going undetected until an advanced stage. More than 70% of patients with gastric cancer develop advanced-stage disease. Esophageal cancer is the 11th most commonly diagnosed cancer and the seventh leading cause of death from cancer worldwide.
Implications of the Results
While the LEAP-015 trial did not show a statistically significant increase in overall survival, the improvement in progression-free survival and objective response rate provides valuable insights for future research. The safety profile of the combination was consistent with that observed in previously reported studies. These results contribute to the scientific community’s collective understanding of these complex diseases and add to the body of knowledge in oncology research.
"Locally advanced unresectable or metastatic gastroesophageal adenocarcinoma remains a challenging disease to treat and a leading cause of cancer death worldwide," said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. "These study results add to our understanding of this combination and will inform our future research as we strive to improve outcomes for more patients with cancer."
