Merck Gets US FDA Approval for Keytruda Plus Pemetrexed & Platinum Chemotherapy

Merck Gets US FDA Approval for Keytruda Plus Pemetrexed & Platinum Chemotherapy

By, Admin 19 September 2024

Merck gets US FDA approval for Keytruda plus pemetrexed & platinum chemotherapy to treat unresectable advanced or metastatic MPM

Overview

Merck, known as MSD outside of the United States and Canada, announced the US Food and Drug Administration (FDA) has approved Keytruda, Merck’s anti-PD-1 therapy, in combination with pemetrexed and platinum chemotherapy, for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

Behind the Approval

  • The approval is based on data from the pivotal phase 2/3 IND.227/KEYNOTE-483 trial. 
  • In IND.227/KEYNOTE-483, Keytruda plus chemotherapy demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; p=0.0162) compared to chemotherapy alone at the trial’s pre-specified final analysis. 
  • Median OS was 17.3 months (95% CI, 14.4-21.3) for Keytruda plus chemotherapy versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. 
  • Keytruda plus chemotherapy also significantly improved progression-free survival (PFS) versus chemotherapy alone (HR=0.80 [95% CI, 0.65-0.99], p=0.0194; median PFS 7.1 months [95% CI, 6.9-8.1] versus 7.1 months [95% CI, 6.8-7.7], respectively). 
  • Overall response rate (ORR) was significantly higher for Keytruda plus chemotherapy versus chemotherapy alone (52% [95% CI, 45.5-59.0] versus 29% [95% CI, 23.0-35.4], respectively; p<0.00001). 
  • Adverse reactions occurring in patients with MPM were generally similar to those in other patients receiving Keytruda in combination with pemetrexed and platinum chemotherapy.

Adverse Reactions Related to Keytruda

  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. 
  • Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection, and complications of allogeneic hematopoietic stem cell transplantation. 
  • Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. 
  • Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda. 
  • Based on the severity of the adverse reaction, Keytruda should be withheld or permanently discontinued and corticosteroids administered if appropriate. 
  • Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.

Statement from Merck Research Laboratories

  • We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma, a disease where prognoses are generally poor,” said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. 
  • This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumours.

The IND.227/KEYNOTE-483 Trial

  • IND.227/KEYNOTE-483 is a multicenter, randomized, open-label, active-controlled Phase 2/3 trial (ClinicalTrials.gov, NCT02784171 ) sponsored and conducted by CCTG in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). 
  • Merck provided Keytruda and support for the trial, which investigated the efficacy and safety of Keytruda in combination with pemetrexed and platinum chemotherapy. 
  • The phase 3 component of the trial enrolled 440 patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease, regardless of tumour PD-L1 expression. 
  • Patients with autoimmune disease that required systemic therapy within three years of treatment or a medical condition that required immunosuppression were ineligible.

Trial Procedure

  • Patients were randomized (1:1) to one of the following treatment arms; all study medications were administered via intravenous infusion:
  • Keytruda (200 mg) with pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) or carboplatin (AUC 5-6 mg/mL/min) on Day 1 of each 21-day cycle for up to six cycles, followed by Keytruda (200 mg) every three weeks [Q3W]. Keytruda was administered prior to chemotherapy on Day 1.
  • Pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) or carboplatin (AUC 5-6 mg/mL/min) on Day 1 of each 21-day cycle for up to six cycles.

Keytruda: Treatment & Outcomes

  • Treatment with Keytruda continued until disease progression as determined by the investigator according to modified RECIST 1.1 for mesothelioma (mRECIST), unacceptable toxicity, or a maximum of 24 months. 
  • Assessment of tumor status was performed every six weeks for 18 weeks, followed by every 12 weeks thereafter. 
  • The main efficacy outcome measure was OS. Additional efficacy outcome measures were PFS, ORR, and duration of response (DoR), as assessed by blinded independent central review (BICR) according to mRECIST.
  • The trial demonstrated a statistically significant improvement in OS, PFS, and ORR in patients randomized to Keytruda in combination with chemotherapy compared with patients randomized to chemotherapy alone.

The 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 mesothelioma diagnosed and more than 25,000 deaths from the disease in 2022. 
  • 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 can progress rapidly, and the five-year survival rate for all stages for cases diagnosed in the U.S. from 2014-2020 was 12.8%.

About Keytruda

  • 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 tumour 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 tumour cells and healthy cells.

Merck’s Immuno-oncology Program

  • 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 programme 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 with Pemetrexed and Platinum Chemotherapy

Keytruda, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

Merck for Cancer Therapy

  • At Merck, the company committed to supporting accessibility to our cancer medicines. 
  • Merck provides multiple programs to help appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. 
  • The Merck Access Programme provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients.
  • Merck is committed to helping provide patients and their caregivers support throughout their treatment with Keytruda. The KEY+YOU Patient Support Program provides a range of resources and support.