Adrixetinib

Courtesy of Kena Betancur/Getty Images With more than 19 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. Keytruda was first approved by the FDA in 2015 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 Merck, 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.

Qurient Co. Ltd. (KRX: 115180), a clinical stage biotech company, today announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for Q901, a small molecule oncology drug candidate targeting cyclin dependent kinase 7 (CDK7). The company plans to enroll up to 70 patients with advanced solid tumors in a Phase 1/2 clinical study taking place in the United States. The goal of the study will be to determine the maximum tolerated dose, dose-limiting toxicities, and the recommended Phase 2 dose of Q901. “IND clearance for Q901 is an important step forward in developing this novel drug candidate that may provide a new alternative treatment to patients with relapsed or refractory malignancies,” says Kiyean Nam, Ph.D., CEO of Qurient. “We look forward to initiating the clinical study for Q901 and presenting additional nonclinical efficacy data of Q901 in various cancer models at an upcoming scientific meeting.” Q901 is a highly selective CDK7 inhibitor that has been shown in in vitro studies to only inhibit CDK7 in the human kinome. CDK7 is a master regulator of cell cycle checkpoints and an essential component of transcription machinery. Additional data from preclinical studies has demonstrated that selective inhibition of CDK7 specifically kills cancer cells with aberrant cell division cycle or transcriptional regulation. Nonclinical pharmacology studies of Q901 have demonstrated that the selective inhibition of CDK7 exerts tumor growth inhibition in a number of murine cell-derived and patient-derived xenograft models, including breast, ovarian, prostate, pancreatic, small-cell lung, and colorectal cancers. Qurient licensed the CDK7 inhibitor program at lead stage from Lead Discovery Center (LDC) and the Max-Planck Society and further optimized the program, completed the IND-enabling studies, and submitted the IND application. “We are thrilled about the second CDK-selective inhibitor from the LDC pipeline to reach cancer patients. The nomination of Q901 for clinical development emphasizes the translational competence of LDC and represents an extremely important milestone,” adds Bert Klebl, CEO and CSO of the LDC. “Starting out with an early-stage and BMBF grant funded academic collaboration with two academic partners, and strongly supported by additional financing from the Max-Planck Foundation, LDC has launched this journey to identify and generate mono-specific CDK7 inhibitors. After an initial animal proof-of-concept, the CDK7 assets were licensed to our strategic collaboration partner, Qurient. We respectfully appreciate our ongoing partnership with Qurient, who are now moving the second joint program, after Q702, forward to clinical trials. While licensing these projects and jointly starting the spin-off, QLi5, we have since built a sustainable and strong partnership with Qurient, with more to come, focusing on the translation of innovative biology and drug discovery programs from LDC’s academic network.” “Qurient has proven to be the ideal partner for this project, and we are more than happy about the results of this strategic partnership,” says Jörn Erselius, Managing Director at Max-Planck Innovation GmbH. The CDK7 inhibitor project and other projects have been supported in part by private sponsors and charities, especially Max-Planck-Foundation, which supports many Max Planck research projects and researchers, including the most recent Nobel Laureates at Max Planck. About Qurient Qurient is a clinical-stage biopharmaceutical company listed in Korea Exchange (KRX 115180). Qurient mainly focuses on development of novel therapeutics from discovery to human proof of concept stages through virtual R&D project management platform. Qurient currently has three programs in clinical development: Q301, a topical leukotriene inhibitor for atopic dermatitis, completed Phase 2b study; Telacebec (Q203), a first-in-class orally available cytochrome bc1 inhibitor for tuberculosis, completed Phase 2 study; and Q702, under Phase 1/2 study. A subsidiary of Qurient, QLi5 is developing immunoproteasome inhibitors targeting multiple Myeloma and diverse other indications. About LDC Lead Discovery Center GmbH was established in 2008 by the technology transfer organization Max Planck Innovation, as a novel approach to capitalize on the potential of excellent basic research for the discovery of new therapies for diseases with high medical need. The Lead Discovery Center takes on promising early-stage projects from academia and transforms them into innovative pharmaceutical leads and antibodies that reach initial proof-of-concept in animals. In close collaboration with high-pro from academia and industry, the Lead Discovery Center is building a strong and growing portfolio of small molecule leads with exceptional medical and commercial potential. The Lead Discovery Center sustains a long-term partnership with the Max Planck Society, KHAN-I GmbH & Co. KG and has formed alliances with Qurient, AstraZeneca, Apeiron, Bayer, Boehringer Ingelheim, Centessa, Merck KGaA, Daiichi Sankyo, Jemincare, Novo Nordisk e.g. In addition, LDC also works with leading translational drug discovery centers and with various investors to provide its assets for company creation. About Max Planck Innovation Max Planck Innovation (MI) is responsible for the technology transfer of the Max Planck Society and, as such, the link between industry and basic research. With an interdisciplinary, team MI advises and supports scientists at Max Planck Institutes in evaluating their inventions, filing patents and founding companies. MI offers industry unique access to the innovations of the Max Planck Institutes. Thus, MI performs an important task: the transfer of basic research results into products that contribute to economic and social progress.