Merck's Blockbuster Cancer Antibody Racks Up Another Approval

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Merck’s blockbuster checkpoint inhibitor Keytruda (pembrolizumab) racked up yet another approval. The U.S. Food and Drug Administration (FDA) approved Keytruda combined with Genentech’s Herceptin (trastuzumab), fluoropyrimidine- and platinum-containing chemotherapy, for first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. It was approved under an accelerated approval pathway based on tumor response rate and durability of response.

“Today’s approval marks an important milestone, as this is the first time an anti-PD-1 therapy has been approved in combination with anti-HER2 therapy and chemotherapy as a first-line treatment for these patients,” said Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “From the start of KEYTRUDA’s development, we have thoughtfully pursued novel combinations to help more patients with cancer. We are pleased to bring a new first-line combination regimen with Keytruda that has shown meaningful improvement in ORR over standard treatment to patients with HER2-positive gastric and GEJ cancer.”

The approval was built on data from the company’s ongoing Phase III KEYNOTE-811 trial, where Keytruda was tested with trastuzumab, which is Genentech’s Herceptin, and either 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin. The trial showed a statistically significant objective response rate (ORR) of 74% for patients who received Keytruda compared to 52% for patients who received just Herceptin and chemotherapy. For the patients receiving Keytruda, the complete response rate was 11% and the partial response rate was 63%, compared to 3.1% and 49% for the Herceptin/chemo combination patients.

The application to the FDA was reviewed under the agency’s Real-Time Oncology Review (RTOR) pilot program.

The interim analysis was evaluated in the first 264 patients randomized. Among those patients, the median age was 62 years, ranging from 19 to 84, 41% were 65 years of age or older, 82% were male, 63% white, 31% Asian and 0.8% Black. Ninety-seven percent of the patients had stage IV metastatic disease and the remaining 3% had locally advanced unresectable disease; 87% of patients’ tumors expressed PD-L1 with a CPS greater than or equal to 1. And 91% had tumors that were not microsatellite instability-high (MSI-H).

The company also reported today that it and partner Eisai’s combination of Keytruda and Lenvima had been accepted and granted priority review for two new approvals by the FDA. The first supplemental Biologics License Application (sBLA) for Keytruda and a supplemental New Drug Application (sNDA) for Lenvima are for first-line treatment of people with advanced renal cell carcinoma (RCC). The priority review was based on progression-free survival (PFS), overall survival (OS), and ORR from the Phase III CLEAR study (KEYNOTE-581/Study307).

The second set of applications are for advanced endometrial carcinoma patients whose disease has progressed after previous systemic therapy in any setting and are not eligible for curative surgery or radiation. This was based on PFS, OS and ORR results from the Phase III KEYNOTE-775/Study 309 trial. They have a target action date of August 25 for the first and September 3 for the second.

“Advanced renal cell carcinoma and advanced endometrial carcinoma are aggressive cancers, and patients urgently need new treatment options that may help improve outcomes,” said Gregory Lubiniecki, vice president, Oncology Clinical Research, Merck Research Laboratories. “We appreciate that the FDA has recognized this significant unmet need and the potential for the combination of Keytruda plus Lenvima in these patients by granting priority review for these applications.”

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