Merck's PD-1 Combination Therapy Receives Full FDA Approval for First-Line Treatment of HER2-Positive Gastric Cancer

Mar 21, 2025 11:36 CST Updated 11:36

MSD

Pharmaceutical R&D and Manufacturer

Recently, the U.S. FDA announced the full approval ofKeytruda (pembrolizumab), the重磅PD-1 inhibitor developed by MSD, in combination with trastuzumab, fluoropyrimidine, and platinum-based chemotherapy,First-line treatment for adult patients with locally advanced unresectable or metastatic HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma.Their tumors express PD-L1 (CPS≥1). Previously, Keytruda received FDA accelerated approval for this indication in 2021.

The efficacy of this combination therapy was evaluated in the KEYNOTE-811 study, a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 698 patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who had not received systemic treatment for metastatic disease. Patients were randomly assigned in a 1:1 ratio to receive either Keytruda or placebo, both in combination with trastuzumab and chemotherapy consisting of either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS) assessed by blinded independent central review (BICR). Additionally, the overall response rate (ORR) and duration of response (DOR) were evaluated. Compared with placebo plus trastuzumab and chemotherapy, the Keytruda combination therapy group demonstrated statistically significant improvements in both OS and PFS.

In patients with PD-L1 CPS≥1,The median PFS in the Keytruda group was 10.9 months compared to 7.3 months in the placebo group.The median OS for the Keytruda group and the control group were 20.1 months and 15.7 months, respectively. The ORR was 73% and 58%, respectively, and the median DOR was 11.3 months and 9.6 months, respectively.

In terms of safety, the adverse event profile of patients receiving Keytruda was consistent with the established safety profile of Keytruda.

HER2 is a tyrosine kinase receptor pro-growth protein expressed on the surface of various tumor cells, including gastric cancer. Approximately one-fifth of gastric cancers are considered HER2-positive. After disease progression in first-line metastatic treatment for HER2-positive gastric cancer, there were previously no HER2-targeted drugs that demonstrated survival benefits in second-line randomized clinical trials.

Positive Overall Results from Phase 3 DESTINY-Gastric04 Study Indicate that [Drug Name] Shows Superiority Compared to Ramucirumab + Paclitaxel as of March 3, 2025Trastuzumab DeruxtecanBrings a statistically significant and clinically meaningful improvement in overall survival (OS) for patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The Independent Data Monitoring Committee observed in the interim analysisTrastuzumab DeruxtecanWith better efficacy, it is recommended to unblind early. Trastuzumab deruxtecan is a DXd antibody-drug conjugate (ADC) targeting HER2, designed with proprietary technology. The drug was developed by Daiichi Sankyo and is jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

Based on the results of the randomized Phase 2 study DESTINY-Gastric01 and two single-arm Phase 2 studies, DESTINY-Gastric02 and DESTINY-Gastric06,Trastuzumab DeruxtecanCurrently approved in more than 65 countries/regions.DESTINY-Gastric04 isTrastuzumab DeruxtecanThe First Phase 3 Study for the Treatment of HER2-Positive Advanced Gastric Cancer.

As for HER2 ADC, other drugs under research and development include Johnson & Johnson's anvatabart opadotin, Hengrui Medicine's trastuzumab deruxtecan (SHR-A1811), CSPC's trastuzumab-MMAE, MiYao Biotech's trastuzumab vedotin, Fosun Pharma's trastuzumab-drug, and Bio-Thera’s BAT-8010, among others.

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