Merck KGaA, Darmstadt, Germany's Cutting-Edge Oncology Pipeline to Enhance Cancer Treatment

Merck KGaA, a prominent science and technology company headquartered in Darmstadt, Germany, has shared significant updates on its oncology pipeline and research initiatives aimed at developing new treatments for cancer patients. This year, Merck plans to commence several Phase Ib and II clinical studies for its promising assets, tuvusertib and M9466, from its comprehensive portfolio of DNA damage response (DDR) inhibitors. The company has also progressed its leading antibody-drug conjugate (ADC), M9140, to Phase Ib trials due to positive clinical benefits and intends to explore additional tumor types. Furthermore, Merck is advancing M3554, another ADC based on its exclusive exatecan-payload technology, into clinical development. These developments were announced during the company’s Oncology R&D Update Call.

Merck KGaA is committed to enhancing its early-stage clinical pipeline of ADCs and DDR inhibitors, driven by encouraging data, particularly regarding M9140 and tuvusertib. The recent addition of M9466 to the pipeline underscores the company’s focus on synergistic oncology approaches, with potential for combination therapies involving tuvusertib and other modalities. Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for Merck’s Healthcare business sector, emphasized the company’s strengths in preclinical ADC research, DDR inhibitors, next-generation immuno-oncology compounds, and oncogenic signaling assets. He reiterated Merck’s commitment to improving outcomes for cancer patients through continued innovation.

Merck's leading DDR inhibitors are being examined under core hypotheses, including synthetic lethality, immune response activation, and synergy with cytotoxic drugs, to identify effective combinations and pinpoint cancer types that might respond best to these treatments. The investigational DDR inhibitors in clinical trials include tuvusertib, a potentially top-tier small-molecule oral ATR kinase inhibitor; M9466, a selective PARP1 inhibitor recently licensed from Jiangsu Hengrui Pharmaceuticals; lartesertib, an ATM kinase inhibitor; and peposertib, a DNA-PK inhibitor. Recent data provide the basis for Phase II combination studies involving tuvusertib and illustrate its potential in combination therapies for PARP-pretreated ovarian cancer.

For M9466, data from the 2024 ASCO Annual Meeting revealed favorable safety and promising efficacy in PARP-sensitive tumors, bolstering Merck’s plans to further develop this investigational drug in various combinations. The newly initiated DDRiver 501 study will evaluate M9466 in combination with tuvusertib in solid tumors with relevant mutations and/or prior PARP inhibitor exposure, focusing on castration-resistant prostate and ovarian cancers. This program aims to expand the list of cancers responsive to first-generation PARP inhibitors.

Merck has also developed an exatecan-based ADC technology platform, with M9140 being the first to reach clinical development. M9140 targets CEACAM5, a protein highly expressed in several tumor types, and incorporates an exatecan payload released specifically within tumors. The first-in-human data from the PROCEADE-CRC-01 clinical trial presented at the 2024 ASCO Annual Meeting showed promising clinical activity and a predictable safety profile for M9140. Following dose optimization, Merck plans to explore combinations with standard-of-care agents in colorectal cancer and launch a broader study in early 2025 to investigate M9140 in other tumors with high CEACAM5 expression.

M3554, another ADC based on Merck’s platform linking an exatecan payload with an anti-GD2 antibody, is set to begin its first-in-human trial in 2024. It will be investigated in patients with solid tumors characterized by high GD2 prevalence, such as neuroblastoma, soft tissue sarcoma, glioblastoma, and osteosarcoma.

Merck’s ongoing research in ADCs, coupled with its preclinical efforts to discover novel antigens and immune agonist ADCs, is expected to expand its clinical ADC portfolio significantly in the coming years. Recent strategic collaborations and agreements further support Merck’s oncology strategy, aligning with its goal to drive the majority of future launches through external innovation.

In summary, Merck KGaA, Darmstadt, Germany, continues to make strides in oncology research, aiming to develop innovative treatments that improve the futures of people with cancer through a robust pipeline of DDR inhibitors and ADCs.