Merck KGaA's Oncology Pipeline Set to Advance Cancer Treatment

Merck KGaA, a prominent science and technology company headquartered in Darmstadt, Germany, has shared significant updates on its oncology pipeline and its comprehensive research and development initiatives. Operating as EMD Serono in the US and Canada, the company is advancing several promising cancer treatments with the potential to greatly impact patient outcomes.

This year, the company plans to initiate multiple new Phase Ib and II clinical studies for its DNA damage response (DDR) inhibitors, including tuvusertib and M9466. Tuvusertib, a potential best-in-class ATR inhibitor, and M9466, a next-generation PARP1 inhibitor recently licensed from Jiangsu Hengrui Pharmaceuticals, are among the key assets in their portfolio. The company’s lead antibody-drug conjugate (ADC), M9140, which has shown positive clinical benefit, has advanced to Phase Ib and is anticipated to be explored in additional tumor types beginning in 2025. Another ADC, M3554, leveraging Merck’s novel exatecan-based technology, is set to enter first-in-human studies in adults in 2024 and pediatric patients in 2025.

Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for Merck KGaA's Healthcare business sector, highlighted the company’s progress in developing ADCs and DDR inhibitors. Encouraging data, particularly for M9140 and tuvusertib, underscore the potential of their early-stage clinical pipeline. The addition of M9466 enhances their focus on synergistic oncology approaches, with the potential for combination therapies involving tuvusertib and other modalities.

Merck KGaA’s pipeline of DDR inhibitors is being investigated across various core hypotheses, including synthetic lethality, immune response activation, and cytotoxic drug synergy. This research aims to identify effective combinations and determine which cancers are most responsive to different treatment regimens. The DDR inhibitor pipeline includes tuvusertib, M9466, lartesertib (an ATM kinase inhibitor), and peposertib (a DNA-PK inhibitor).

Recent data from the DDRiver 301 Part B study, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated the potential of combining tuvusertib with the PARP inhibitor niraparib in PARP-pretreated ovarian cancer. Additional studies, including the DDRiver NSCLC 322, DDRiver EOC 302, and JAVELIN DDRiver Bladder, are exploring tuvusertib in combination with other agents across various cancer types.

For M9466, data from Hengrui’s first-in-human clinical trial presented during the 2024 ASCO Annual Meeting indicated a favorable safety profile and promising efficacy in PARP-sensitive tumors. The recently opened DDRiver 501 study will evaluate M9466 in combination with tuvusertib in solid tumors with relevant mutations, particularly focusing on castration-resistant prostate and ovarian cancers.

The company’s exatecan-based ADC M9140, targeting CEACAM5-expressing tumors, has shown high bystander activity in preclinical research and promising results in early human trials. Following dose optimization, Merck plans to assess M9140 in combination with standard-of-care agents for colorectal cancer. A basket trial scheduled for early 2025 will explore M9140 monotherapy in tumors with high CEACAM5 expression.

M3554, another ADC from Merck’s platform, links an exatecan payload with an anti-GD2 antibody and is set to enter clinical trials later in 2024. It will be evaluated in patients with solid tumors with high GD2 prevalence, such as neuroblastoma, soft tissue sarcoma, glioblastoma, and osteosarcoma.

Merck KGaA continues to drive innovation in oncology through external collaborations. Recent agreements with Caris Life Sciences, Inspirna, and Abbisko Therapeutics support their strategy of leveraging external innovation to develop first-in-class ADCs and other novel cancer treatments.

Merck KGaA’s commitment to improving cancer care is evident in its robust research efforts aimed at creating effective and innovative treatments. The company’s vision is to transform more cancer patients into cancer survivors, underscoring its dedication to advancing the future of cancer care.