Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and the Canadian Cancer Trials Group (CCTG) today announced that the Phase 2/3 CCTG IND.227/KEYNOTE-483 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy met its primary endpoint of overall survival (OS) for the first-line treatment of patients with unresectable advanced or metastatic malignant pleural mesothelioma. IND.227 was sponsored by CCTG, in collaboration with investigators in Italy (co-sponsored by National Cancer Institute of Naples – NCIN), and France (co-sponsored by The French Cooperative Thoracic Intergroup – IFCT); Merck provided KEYTRUDA and support for the trial. At the final analysis of the study, KEYTRUDA plus chemotherapy showed a statistically significant and clinically meaningful improvement in OS compared to chemotherapy alone in these patients. The safety profile of KEYTRUDA in combination with chemotherapy in this study was consistent with previously reported studies. Results will be presented at an upcoming medical meeting and discussed with regulatory authorities worldwide.
“Malignant pleural mesothelioma is a rapidly progressing cancer that develops in the lining of the lungs and has a poor prognosis,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Patients are in need of new treatments that can improve survival outcomes, and these positive results support the potential of KEYTRUDA in combination with chemotherapy as a first-line treatment for patients with the most common form of malignant mesothelioma.”
“There have been few treatment advances for patients with malignant pleural mesothelioma, which can be challenging to treat through surgery and radiation alone,” said Dr. Quincy Chu, CCTG’s study chair of the IND.227 trial/KEYNOTE-483 trial. “The results from the trial have the potential to make a difference for patients with this disease who have had limited treatment options available to them.”
Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations.
IND.227/KEYNOTE-483 is a randomized, open-label, randomized Phase 2/3 trial (ClinicalTrials.gov, NCT02784171) sponsored and conducted by the Canadian Cancer Trials Group (CCTG) in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Support for the trial was provided by Merck. The trial evaluated KEYTRUDA in combination with chemotherapy for the treatment of patients with unresected advanced malignant pleural mesothelioma. The primary endpoint of the study is OS, and secondary endpoints include progression-free survival (PFS) and objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 modified for mesothelioma, safety and quality of life. The Phase 3 part of the trial enrolled 440 patients who were randomized to receive:
- KEYTRUDA (200 mg every three weeks for up to 35 cycles) in combination with pemetrexed (500 mg/m2 every three weeks for six cycles) and cisplatin (75 mg/m2 every three weeks for six cycles; carboplatin substitution was permitted), or
- Pemetrexed and cisplatin (carboplatin substitution was permitted) alone.
About malignant mesothelioma
Malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. Worldwide, it is estimated there were more than 30,000 new cases of malignant mesothelioma diagnosed and more than 26,000 deaths from the disease in 2020. Pleural mesothelioma, which develops in the lining of the lungs, is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Malignant pleural mesothelioma often progresses rapidly, and the five-year survival rate is only 12%. Although incidence of malignant mesothelioma has gradually declined in the United States, continued use of and exposure to asbestos around the world has resulted in increasing global rates of this aggressive disease.
About the Canadian Cancer Trials Group
The Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From their operations centre at Queen’s University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society and their aim is to improve survival and quality of life for all people with cancer. CCTG IND.227 was supported by a grant from the Canadian Cancer Society (CCS) (707213). For further information, please visit the CCTG website: www.cctg.ca.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
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.
Merck’s focus on cancer
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.