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Merck Presents Three-Year Survival Data for Keytruda (pembrolizumab) in Combination With Chemotherapy and Updated Phase 1/2 Data for Investigational Quavonlimab (MK-1308) in Combination With Keytruda in Advanced Non‑Small Cell Lung Cancer

KENILWORTH, N.J.--(BUSINESS WIRE) October 16, 2020 -- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced positive results from two studies from the company’s leading lung cancer clinical development program evaluating Keytruda, Merck’s anti-PD-1 therapy: Keytruda in combination with chemotherapy (KEYNOTE-021 [Cohort G]) and Keytruda in combination with quavonlimab (MK-1308), Merck’s novel investigational anti-CTLA-4 antibody.

In KEYNOTE-021 (Cohort G), first-line treatment with Keytruda in combination with chemotherapy (n=60) demonstrated a significant improvement in objective response rates (58% vs. 33%), progression-free survival (HR=0.54 [95% CI, 0.35-0.83]) and a sustained, long-term survival benefit (HR=0.71 [95% CI, 0.45-1.12]) versus chemotherapy alone (n=63) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) regardless of PD‑L1 expression (Featured Poster #OFP01.02). Patients in Cohort G had no EGFR or ALK genomic tumor aberrations. These findings represent the longest follow-up data for an anti-PD-1/PD‑L1 therapy in combination with chemotherapy for the first-line treatment of NSCLC. Additionally, updated follow-up data from a Phase 1/2 study of quavonlimab in combination with Keytruda showed encouraging anti-tumor activity and an acceptable safety profile as first-line treatment in patients with advanced NSCLC (Poster #TS01.02).

“Over the last five years, Keytruda has become foundational in the treatment of metastatic lung cancer. The long-term data from KEYNOTE-021 (Cohort G) reinforce the use of Keytruda in combination with chemotherapy in certain advanced lung cancer patients, while data from our oncology pipeline reflect our commitment to exploring a number of new combinations with Keytruda that we believe could have a meaningful impact for more lung cancer patients,” said Dr. Vicki Goodman, vice president, oncology clinical research, Merck Research Laboratories. “Updated data from our anti-CTLA-4 antibody quavonlimab in combination with Keytruda support the continued development of this new combination and a Phase 3 study of quavonlimab coformulated with Keytruda in advanced non-small cell lung cancer is planned.”

Results from both studies were presented at the IASLC 2020 North America Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer on Friday, Oct. 16. Follow Merck on Twitter via @Merck and keep up to date with NACLC news and updates by using the hashtag #NACLC20.

Keytruda in Combination With Chemotherapy: Long-Term Data in Advanced NSCLC From KEYNOTE-021 (Cohort G) (Featured Poster #OFP01.02)
New data from Cohort G of KEYNOTE-021 (NCT02039674) demonstrated a significant improvement in objective response rates (ORR), progression-free survival (PFS) and a sustained, long-term survival benefit with Keytruda in combination with pemetrexed (ALIMTA®) and platinum chemotherapy versus pemetrexed and platinum chemotherapy alone after four years of median study follow-up (49.4 months; range, 43.5 to 55.4). Cohort G of the Phase 1/2, multi-cohort, multi-center, open-label trial evaluated Keytruda in combination with chemotherapy (n=60) versus chemotherapy alone (n=63) as first-line treatment in patients with advanced nonsquamous NSCLC. Patients in Cohort G had no EGFR or ALK genomic tumor aberrations.

Findings from KEYNOTE-021 (Cohort G) showed that 50% of patients treated with Keytruda in combination with chemotherapy were alive at three years versus 37% of patients who received chemotherapy alone. Keytruda in combination with chemotherapy also reduced the risk of death by 29% (HR=0.71 [95% CI, 0.45-1.12]) versus chemotherapy alone, with a median overall survival (OS) of 34.5 versus 21.1 months. The OS benefit was observed despite a 70% (n=43/61) effective crossover rate from chemotherapy to anti‑PD‑1/PD‑L1 therapy, including 28 patients who were treated with Keytruda as part of the on-study crossover.

The ORR was 58% for Keytruda in combination with chemotherapy versus 33% for chemotherapy alone. Keytruda also reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.35-0.83]) versus chemotherapy, with a median PFS of 24.5 months (range, 9.7 to 36.3) versus 9.9 months (range, 6.2 to 15.2). The estimated three-year PFS rate was 37% for patients who received Keytruda in combination with chemotherapy versus 16% for those who received chemotherapy alone. The median duration of response (DOR) was more than one year longer with Keytruda in combination with chemotherapy (36.3 months; range, 1.4+ to 49.3+) versus chemotherapy alone (22.8 months; range, 2.8+ to 47.2+). Additionally, 51% of patients treated with Keytruda in combination with chemotherapy had responses lasting three years versus 47% with chemotherapy alone.

Notably, 92% of patients who completed two years of treatment with Keytruda were alive at three years (n=11/12). All 12 patients experienced an objective response and the estimated three-year DOR rate was 100% (median DOR not reached [NR]; range, 11.7+ to 49.3+ months).

No new safety signals for Keytruda in combination with chemotherapy were identified with long-term follow-up. Among all those treated, 39% of those who received Keytruda in combination with chemotherapy and 31% of those who received chemotherapy alone experienced Grade 3-5 treatment-related adverse events (TRAEs). Grade 3-5 TRAEs that led to discontinuation occurred in 17% of patients who received Keytruda in combination with chemotherapy and 16% of those who received chemotherapy alone. Grade 3-5 TRAEs that led to death occurred in 2% (n=1) of patients who received Keytruda in combination with chemotherapy and 3% (n=2) of those who received chemotherapy alone.

The KEYNOTE-021 (Cohort G) trial was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).

Quavonlimab (anti-CLTA-4) in Combination With KEYTRUDA: Phase 1/2 Results in Advanced NSCLC (Poster #TS01.02)
In this first-in-human, open-label, multi-arm Phase 1/2 study (NCT03179436), quavonlimab, Merck’s novel anti-CTLA-4 therapy, was evaluated in combination with KEYTRUDA as a first-line treatment in patients with advanced NSCLC. In the dose-confirmation phase, patients received quavonlimab (25 mg or 75 mg) every three weeks (Q3W) or every six weeks (Q6W) in combination with KEYTRUDA (200 mg Q3W for up to 35 cycles). The primary objective of the study was safety and tolerability; secondary and exploratory objectives included ORR per RECIST v1.1 by blinded independent central review (BICR), PFS, OS and DOR. Response based on PD-L1 status was retrospectively evaluated using tumor proportion score (TPS) as a continuous variable.

Findings showed that quavonlimab in combination with KEYTRUDA had an acceptable safety profile with no unexpected toxicities and suggested encouraging anti-tumor activity. Any-grade adverse events occurred in 98% of patients; TRAEs occurred 85% of patients. Grade ≥3 TRAEs occurred in 36% of patients across all treatment arms and the most common TRAEs (>10% in any arm) were increased alanine aminotransferase (8%), pneumonitis (8%) and increased aspartate aminotransferase (6%).

With 16.9 months of median follow-up (range, 7.0 to 21.3), results from the study showed the effect of quavonlimab in combination with KEYTRUDA across secondary and exploratory endpoints, including ORR, PFS, OS and DOR. Responses to quavonlimab in combination with KEYTRUDA were observed regardless of PD-L1 expression with higher TPS scores significantly associated with better response (one-sided p=0.015). These safety and efficacy data support the 25 mg Q6W dose as the recommended Phase 2 dose of quavonlimab when used in combination with KEYTRUDA.

 

 

   

Quavonlimab
25 mg Q6W + KEYTRUDA
n=40

 

 

Quavonlimab
25 mg Q3W + KEYTRUDA
n=40

 

 

Quavonlimab
75 mg Q6W + KEYTRUDA
n=40

 

 

Quavonlimab
75 mg Q3W + KEYTRUDA
n=14

 

 

Total
N=134

 
 

ORR, %
(95%, CI)

 

 

37.5
(22.7-54.2)

 

 

40
(24.9-56.7)

 

 

27.5
(14.6-43.9)

 

 

35.7
(12.8-64.9)

 

 

35.1
(27.0-43.8)

 
 

PFS, median
(95%, CI), mo

 

 

7.8
(4.2-14.8)

 

 

6.0
(2.0-8.3)

 

 

6.0
(3.5-8.1)

 

 

3.4
(1.8-NE)

 

 

6.1
(4.2-7.3)

 
 

OS, median
(95%, CI), mo

 

 

18.1
(14.2-NE)

 

 

18.1
(9.1-21.8)

 

 

17.1
(9.0-NE)

 

 

13.7
(3.5-NE)

 

 

16.5
(14.2-21.8)

 
 

DOR, median
(95%, CI), mo

 

 

NR
(4.0 to 21.6+)

 

 

7.9
(2.8 to 21.4+)

 

 

15.9
(3.4 to 21.4+)

 

 

NR
(8.8+ to 16.3+)

 

 

13.6
(2.8 to 21.6+)

 

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10% to 15% of all lung cancers. Before 2014, the five-year survival rate for patients diagnosed in the U.S. with NSCLC and SCLC was estimated to be 5% and 6%, respectively.

About Keytruda (pembrolizumab) Injection, 100 mg

Keytruda is an anti-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 1,200 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 Quavonlimab (MK-1308)

Quavonlimab is a novel humanized IgG1 monoclonal antibody that binds to CTLA-4 and blocks interaction with its ligands, CD80 and CD86. Quavonlimab is currently being evaluated in combination with Keytruda across multiple solid tumors as part of ongoing Phase 1 and 2 trials. A Phase 3 trial of quavonlimab coformulated with Keytruda in advanced non-small cell lung cancer is planned.

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

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2019 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for Keytruda at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for Keytruda at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

Source: Merck & Co., Inc.
 

Posted: October 2020

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