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FDA Approves KEYTRUDA® (pembrolizumab) as Adjuvant Treatment Following Surgical Resection and Platinum-Based Chemotherapy for Patients with Stage IB (T2a ≥4 Centimeters), II, or IIIA Non-Small Cell Lung Cancer (NSCLC)

Approval based on KEYNOTE-091 trial, which demonstrated a clinically meaningful improvement in disease-free survival with KEYTRUDA in these patients following surgical resection and platinum-based chemotherapy versus placebo

Approval marks fifth indication for KEYTRUDA-based regimens in NSCLC and 34th indication for KEYTRUDA in the US

RAHWAY, N.J.–(BUSINESS WIRE)– Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as a single agent, for adjuvant treatment following surgical resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 centimeters [cm]), II, or IIIA non-small cell lung cancer (NSCLC).

The approval is based on data from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS. The major efficacy outcome measure was investigator-assessed disease-free survival (DFS). In patients who received adjuvant platinum-based chemotherapy following surgical resection, KEYTRUDA reduced the risk of disease recurrence or death by 27% (hazard ratio [HR]=0.73 [95% CI, 0.60-0.89]) versus placebo regardless of PD-L1 expression. The median DFS in patients regardless of PD-L1 expression who received adjuvant platinum-based chemotherapy following surgical resection was nearly five years (58.7 months) for the KEYTRUDA arm versus nearly three years (34.9 months) for the placebo arm, translating to a nearly two-year (23.8 months) DFS improvement versus placebo. In an exploratory subgroup analysis of the 167 patients (14%) who did not receive adjuvant chemotherapy, the DFS HR was 1.25 (95% CI, 0.76-2.05).

“While there have been many advances for patients with metastatic disease, surgery remains the typical treatment for people with stage IB, II and IIIA non-small cell lung cancer. Unfortunately, many of these patients who undergo surgery still see their disease return,” said Roy S. Herbst, M.D., Ph.D., deputy director and chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital and ensign professor of medicine (medical oncology) and professor of pharmacology, Yale School of Medicine. “Today’s approval for KEYTRUDA offers a new, important immunotherapy treatment option for stage IB (T2a ≥4 cm), II, or IIIA patients with non-small cell lung cancer following surgery and adjuvant chemotherapy. This provides, for the first time, an adjuvant immunotherapy treatment option for non-small cell lung cancer patients with stage IB disease and regardless of PD-L1 expression.”

The adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.
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, 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. For more information, see “Selected Important Safety Information” below.

“Six years ago, KEYTRUDA was the first anti-PD-1 therapy approved for the first-line treatment of metastatic non-small cell lung cancer and has changed the way metastatic disease is treated. Today’s approval marks the fifth indication for KEYTRUDA in non-small cell lung cancer and the first indication for KEYTRUDA in patients with resected stage IB (T2a ≥4 cm), II, or IIIA disease following adjuvant chemotherapy,” said Dr. Gregory Lubiniecki, vice president, oncology global clinical development, Merck Research Laboratories. “This is an important milestone as we continue our efforts to pursue meaningful advances for patients with non-small cell lung cancer.”

With this approval, KEYTRUDA is the only immunotherapy with an approved option for NSCLC regardless of PD-L1 expression in both the adjuvant and metastatic settings. In addition to today’s approval in the adjuvant setting, KEYTRUDA is indicated in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations; in combination with carboplatin and either paclitaxel or paclitaxel protein-bound for the first-line treatment of patients with metastatic squamous NSCLC; as a single agent 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 stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic; and as a single agent 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.

Study design and additional data supporting the approval

KEYNOTE-091/EORTC-1416-LCG/ETOP-8-15 – PEARLS (ClinicalTrials.gov, NCT02504372) is a multicenter, randomized, triple-blind, placebo-controlled Phase 3 trial conducted in 1,177 patients with completely resected stage IB (T2a ≥4 cm), II, or IIIA NSCLC per the American Joint Committee on Cancer (AJCC) seventh edition. Patients had not received neoadjuvant radiotherapy or chemotherapy. Adjuvant chemotherapy up to four cycles was optional. Patients were ineligible if they had active autoimmune disease, were on chronic immunosuppressive agents or had a history of interstitial lung disease or pneumonitis.

Patients were randomized (1:1) to receive KEYTRUDA 200 mg or placebo intravenously every three weeks. Treatment continued until RECIST v1.1-defined disease recurrence as determined by the investigator, unacceptable toxicity or up to one year. Tumor assessments were conducted every 12 weeks for the first year, then every six months for years two to three, and then annually through year five. After year five, imaging was performed as per local standard of care. The major efficacy outcome measure was investigator-assessed DFS. An additional efficacy outcome was overall survival.

Of 1,177 patients randomized, 1,010 (86%) received adjuvant platinum-based chemotherapy following resection.

In the study, the median duration of exposure to KEYTRUDA was 11.7 months (range, 1 day to 18.9 months). Sixty-eight percent of patients in the KEYTRUDA arm were exposed to KEYTRUDA for ≥6 months.

The trial met its primary endpoint, demonstrating a statistically significant improvement in DFS in the overall population for patients randomized to the KEYTRUDA arm compared to patients randomized to the placebo arm. Overall survival results were not mature with only 42% of pre-specified OS events in the overall population.

KEYNOTE-091/EORTC-1416-LCG/ETOP-8-15 – PEARLS was conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP).

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.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible got screened for lung cancer in 2021.

About Merck

Merck, known as MSD outside of the United States and Canada, has been developing important medicines and vaccines for more than 130 years, and aspires to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Merck’s focus on cancer

Merck’s goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. 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. For more information about Merck’s oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck’s research in lung cancer

Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has five approved U.S. indications (see indications below) and is approved for advanced disease in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.

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