With 33 approvals from the FDA, Merck’s checkpoint inhibitor Keytruda has become a powerhouse oncology drug and is likely to continue to rack up more regulatory wins.
Courtesy of Kena Betancur/Getty Images
With 33 approvals from the FDA across 16 tumor types, Merck’s checkpoint inhibitor Keytruda has become a powerhouse oncology drug and is likely to continue to rack up more regulatory wins.
Keytruda was first approved by the FDA in 2014 and has become the cornerstone oncology drug for Merck. Last year, Keytruda (pembrolizumab) generated more than $17 billion for Merck, making it the second best-selling drug globally. The medication is slated to become the world’s top-selling drug by 2025, according to analyst predictions.
Merck continues to run its own programs assessing Keytruda, and multiple companies are also testing the medication in concert with their own assets.
BioSpace outlines some of the more recent announcements regarding Keytruda combinations.
Seagen-Astellas Pair Keytruda with Padcev for Urothelial Cancer
At the European Society of Medical Oncology, Merck and partners Seagen and Astellas Pharma touted data from the cohort K of the Phase Ib/II EV-103 trial (KEYNOTE-869) evaluating Keytruda with bladder cancer drug Padcev (enfortumab vedotin-ejfv) as a first-line treatment for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy.
Cohort data showed patients who received the combination saw a 64.5% confirmed objective response rate. Of those, 10.5% of patients experienced a complete response, and 53.9% saw a partial response. The median duration of response was not reached.
Additionally, the companies noted that in the combination arm, median progression-free survival was not reached. Median overall survival was 22.3 months. For patients who received Padcev alone, median PFS was eight months and median OS was 21.7 months.
Marjorie Green, head of late-stage development at Seagen, noted in the announcement that nearly 65% of patients who received the combination study benefitted. Almost 11% showed no detectable cancer following treatment, she said.
Jonathan E. Rosenberg, chief of genitourinary medical oncology service at Memorial Sloan Kettering, expressed his agreement, saying the combination could become an important therapeutic option for patients.
Two years ago, the FDA granted the combination of Padcev and Keytruda Breakthrough Therapy designation for this indication. The companies said in a joint announcement that the data warrants further investigation for this patient line.
Qurient Pairs Keytruda with its CDK7 Inhibitor
Earlier this week, South Korea-based Qurient Co. Ltd. announced an agreement with Merck that pairs Keytruda with that company’s asset, Q901, a selective CDK7 inhibitor. Financial terms were not disclosed. Qurient is planning a Phase I/II study to assess the combination for the treatment of selected advanced solid tumors.
It’s the second Qurient asset to be paired with Keytruda. The company is also assessing Keytruda with another one of its products, Q702.
Kiyean Nam, chief executive officer of Qurient, said Q901 has shown “very effective tumor growth inhibition” through cell cycle regulation that triggers genomic instability. Nam noted that may “set synthetic lethality for anti-PD-1 therapy.”
“The Q901 and anti-PD-1 antibody combination showed a beneficial effect in preclinical models, and we expect the same clinical benefits,” Nam said in a statement.
Medicenna Looks to Keytruda
Canada-based Medicenna Therapeutics also struck a Keytruda-centric deal with Merck this week. The company aims to study its beta-only, long-acting IL-2 super-agonist MDNA11 with Keytruda in a Phase I/II study.
The ABILITY study will assess the pharmacokinetics, pharmacodynamics and preliminary efficacy of MDNA11 as a monotherapy and in combination with Keytruda in patients with advanced/metastatic solid tumors. The partnership between the companies includes the establishment of a Joint Development Committee that aims to advance the trial’s combination arm.
MDNA11 is designed to selectively expand CD8 T and NK cells and increase PD-1 expression on immune cells.
Fahar Merchant, president and CEO of Medicenna, said the agreement offers the opportunity to work with Merck, “the world’s leading immuno-oncology company.”
The company believes MDNA11 has significant potential as a stand-alone treatment. Merchant stated that combining it with Keytruda “may significantly enhance therapeutic benefit in different types of cancer, potentially maximizing the value of MDNA11.”
Keytruda Combination in Prostate Cancer
Data recently published in the Annals of Oncology and shared at ESMO revealed that Keytruda, in combination with standard of care abiraterone acetate and prednisone, produces anti-tumor activity in patients with metastatic castration-resistant prostate cancer who had not previously received chemotherapy for their cancer.
According to the data, 56.3% of patients who received Keytruda in combination with standard of care achieved a confirmed prostate-specific antigen response. Additionally, the data shows that 81 of the 103 patients, 78.6%, saw a PSA reduction from baseline. This suggests adding Keytruda to the treatment regimen is safe and effective, the study authors wrote.
