RAHWAY, NJ, USA I December 18, 2023 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the European Commission (EC) has approved two new indications for KEYTRUDA, Merck’s anti-PD-1 therapy, in gastrointestinal cancers:
These approvals by the EC follow positive recommendations from the Committee for Medicinal Products for Human Use received in October 2023 and November 2023 and were based on overall survival (OS) results from the Phase 3 KEYNOTE-859 and KEYNOTE-966 trials, respectively.
In KEYNOTE-859, KEYTRUDA plus chemotherapy significantly improved OS in the overall patient population, reducing the risk of death by 22% (HR=0.78 [95% CI, 0.70-0.87]; p
In KEYNOTE-966, KEYTRUDA plus chemotherapy demonstrated a statistically significant improvement in OS, reducing the risk of death by 17% (HR=0.83 [95% CI, 0.72-0.95]; one-sided p=0.0034) compared to chemotherapy alone at the trial’s pre-specified final analysis for OS. Median OS was 12.7 months (95% CI, 11.5-13.6) for KEYTRUDA plus chemotherapy versus 10.9 months (95% CI, 9.9-11.6) for chemotherapy alone.
The safety of KEYTRUDA plus chemotherapy has been evaluated in 4,787 patients across tumor types. In KEYNOTE-859, the incidence of Grade 3-5 adverse reactions in patients with gastric cancer was 75% for KEYTRUDA plus chemotherapy and 70% for chemotherapy. In KEYNOTE-966, the incidence of Grade 3-5 adverse reactions in patients with BTC was 85% for KEYTRUDA plus chemotherapy and 84% for chemotherapy alone.
These approvals allow marketing of these KEYTRUDA regimens for these indications in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. With these decisions, KEYTRUDA is now approved for 26 indications in the EU, including seven in gastrointestinal cancers.
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal and colorectal cancers.
About KEYNOTE-859
KEYNOTE-859 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov NCT03675737) evaluating KEYTRUDA in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. The primary endpoint is OS, and secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety. The trial enrolled 1,579 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) in combination with fluoropyrimidine- and platinum-containing chemotherapy, or placebo in combination with chemotherapy.
About KEYNOTE-966
KEYNOTE-966 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov NCT04003636) evaluating KEYTRUDA in combination with gemcitabine and cisplatin compared to placebo plus gemcitabine and cisplatin for the first-line treatment of advanced or unresectable BTC. The primary endpoint is OS, and the secondary endpoints include PFS, ORR, DOR and safety. The trial enrolled 1,069 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) plus gemcitabine and cisplatin, or placebo plus gemcitabine and cisplatin.
Gastric (stomach) cancer tends to develop slowly over many years and rarely causes early symptoms, resulting in most patients presenting with advanced stage disease. Overall, more than 70% of patients with gastric cancer develop advanced-stage disease. Most gastric cancers are adenocarcinomas (about 90% to 95%), which develop from cells in the innermost lining of the stomach (known as the mucosa). More than half of patients with gastric cancer have tumors expressing PD-L1 (CPS ≥1), and the majority of gastric cancers are HER2-negative, affecting approximately four out of every five patients. Gastric cancer is the fifth most diagnosed cancer and the fourth leading cause of cancer death worldwide, with approximately 1.1 million patients diagnosed and 768,000 patient deaths from the disease globally in 2020. The five-year survival rate for patients diagnosed with gastric cancer at an advanced stage is only 6%.
Biliary tract cancer is a group of rare and highly aggressive cancers in the liver, gallbladder and bile ducts. Biliary tract cancer is the second most common type of primary liver cancer after hepatocellular carcinoma, accounting for approximately 15% of all liver cancers. It is estimated there are approximately 211,000 patients diagnosed with BTC and 174,000 patient deaths from the disease each year globally. Biliary tract cancer is most frequently diagnosed in patients between 50 and 70 years old, and approximately 70% of BTC patients are diagnosed at an advanced stage. Patients diagnosed with BTC face a very poor prognosis, with a five-year relative survival rate of 5-15% across all patients.
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal (GEJ) adenocarcinoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
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