KEYNOTE-716 is the first Phase 3 trial with an anti-PD-1/L1 to significantly improve distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) for these patients
Based on KEYNOTE-716, KEYTRUDA received US FDA approval and a positive EU CHMP opinion for the adjuvant treatment of patients aged 12 and older with completely resected stage IIB and IIC melanoma
RAHWAY, NJ, USA I June 05, 2022 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced distant metastasis-free survival (DMFS) results from the Phase 3 KEYNOTE-716 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, versus placebo as adjuvant therapy for patients with resected stage IIB or IIC melanoma. With a median follow-up of 27.4 months, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in DMFS versus placebo (HR=0.64 [95% CI, 0.47-0.88]; p=0.0029). Median DMFS was not reached in either arm. These late-breaking data are being presented for the first time today at 10:45 a.m. ET during an oral abstract session at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA9500).
Additionally, at the median 27.4-month follow-up, KEYTRUDA continued to show a reduction in the risk of recurrence versus placebo (HR=0.64 [95% CI, 0.50-0.84]). According to Kaplan-Meier estimates, 81.2% of patients in the KEYTRUDA arm were recurrence-free at two years compared to 72.8% of patients in the placebo arm. A prespecified exploratory analysis of health-related quality of life (HRQoL) from KEYNOTE-716 will also be presented at ASCO 2022 on Monday, June 6 (abstract #9581), showing HRQoL was similar between the KEYTRUDA and placebo arms based on EORTC Quality of Life Questionnaire Core 30 or EQ-5D-5L VAS scores.
“Patients with stage IIB and IIC melanoma are at risk of seeing their cancer return and spread to distant sites,” said Dr. Georgina Long, co-medical director, Melanoma Institute Australia (MIA), and chair, Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, University of Sydney. “The latest results from KEYNOTE-716 show the potential of pembrolizumab to help reduce distant recurrence in patients with resected stage IIB and IIC melanoma, and further highlight the important role of adjuvant therapy for these patients.”
In the study, the safety profile of KEYTRUDA was consistent with previously reported studies in patients with solid tumors, and no new safety signals were observed at the time of DMFS analysis. Treatment-related adverse events Grade 3 or higher were observed in 17% of patients receiving KEYTRUDA versus 5% of patients receiving placebo. Immune-mediated events and infusion reactions were higher with KEYTRUDA (38% vs 9%, respectively).
“Based on survival data, we know that patients with stage IIB and IIC melanoma have similar five-year outcomes as those with stage IIIB melanoma,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “In KEYNOTE-716, treatment with KEYTRUDA after surgery improved both distant metastasis-free survival and recurrence-free survival compared to placebo in patients with stage IIB or IIC melanoma. These data are encouraging for the melanoma community and add to results from six positive pivotal studies for KEYTRUDA-based regimens in earlier stages of cancer.”
In addition to KEYNOTE-716, the five other pivotal trials evaluating a KEYTRUDA-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials include: KEYNOTE-091 in stage IB (≥4 centimeters) to IIIA non-small cell lung cancer; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer.
Based on RFS results from KEYNOTE-716, the U.S. Food and Drug Administration approved KEYTRUDA for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB or IIC melanoma following complete resection in December 2021. With the approval, KEYTRUDA became the first anti-PD-1 adjuvant treatment option for patients (12 years and older) across completely resected stage IIB, IIC and III melanoma. The European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion based on KEYNOTE-716 in May 2022, and the data will be shared with additional health authorities globally.
A compendium of Merck’s presentations and posters is available here. Please visit https://www.merck.com/media/merck-at-asco-2022 and @Merck on Twitter to keep up to date with ASCO news and updates.
KEYNOTE-716 study design and additional data
KEYNOTE-716 (ClinicalTrials.gov, NCT03553836) is a randomized, double-blind Phase 3 trial that enrolled 976 adult and pediatric patients (12 years and older) with resected stage IIB or IIC melanoma. Following complete surgical resection, patients were randomized to KEYTRUDA 200 mg for adult patients and 2 mg/kg (up to 200 mg) for pediatric patients or placebo every three weeks for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint was RFS, and secondary endpoints included DMFS and overall survival. Overall survival will continue to be followed for upcoming analyses.
As of data cutoff for the third interim analysis (Jan. 4, 2022), the median study follow-up was 27.4 months. Distant metastasis-free survival was defined as time from randomization to the first diagnosis of distant metastasis. In the KEYTRUDA arm, 12.9% (n=63/487) of patients experienced a DMFS event versus 19.4% (n=95/489) of patients in the placebo arm. The estimated two-year DMFS rates were 88.1% with KEYTRUDA versus 82.2% with placebo.
As previously announced, the study met the primary endpoint of RFS at the first interim analysis (HR=0.65 [95% CI, 0.46-0.92]; p=0.00658). At the third interim analysis, 19.5% (n=95/487) of patients who received KEYTRUDA experienced an RFS event versus 28.4% (n=139/489) of patients who received placebo. At two years, the estimated RFS rates were 81.2% with KEYTRUDA versus 72.8% with placebo.
About Merck’s research in melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases diagnosed worldwide in 2020. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be nearly 100,000 new cases of melanoma diagnosed and almost 8,000 deaths resulting from the disease in the U.S. in 2022.
The recurrence rates for resected melanoma are estimated to be 32-46% for patients with stage IIB and stage IIC disease and 39-74% for patients with stage III disease. The five-year survival rates (AJCC eighth edition) are estimated to be 87% for stage IIB, 82% for stage IIC, 93% for stage IIIA, 83% for stage IIIB, 69% for stage IIIC and 32% for stage IIID.
Merck is committed to delivering meaningful advances for patients with melanoma with KEYTRUDA and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of adult patients with resected stage III melanoma and is approved in over 90 countries based on the results from EORTC1325/KEYNOTE-054. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.
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 1,700 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
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.
Additional Selected KEYTRUDA Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
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:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
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.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
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.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors 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. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
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.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (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 cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 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.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
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.
Endometrial Carcinoma
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.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] 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. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
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.
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.
About Merck
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 Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
