- Potential best-in-class ATR inhibitor tuvusertib being explored in Phase II combination clinical studies; recently licensed PARP1 inhibitor M9466 to be evaluated in Phase Ib combination dose-finding studies
- Potential first-in-class anti-CEACAM5 ADC with an exatecan payload, M9140, which entered Phase Ib in colorectal cancer this year, to be explored in other CEACAM5-expressing tumors beginning in 2025
- First-in-class anti-GD2 ADC M3554, leveraging company's novel exatecan-based technology, set to enter first-in-human study in adults in 2024 and in pediatric patients in 2025
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DARMSTADT, Germany--BUSINESS WIRE--
Merck, a leading science and technology company, today shared updates on the company's oncology pipeline and focused approach to the research and development of potential new medicines designed to improve the futures of people with cancer. This year, the company plans to open multiple new Phase Ib and II clinical studies for tuvusertib and M9466, key assets from its broad portfolio of DNA damage response (DDR) inhibitors; has advanced its lead antibody-drug conjugate (ADC), M9140, to Phase Ib based on positive signs of clinical benefit, and plans to expand to additional tumors; and progress M3554, its next ADC based on the company's proprietary exatecan-payload platform, into clinical development. These and other updates were shared at the company's Oncology R&D Update Call.
"The advancements in our strong early-stage clinical pipeline of ADCs created with our in-house platform and DDR inhibitors are grounded in encouraging data, particularly for M9140 and tuvusertib. The addition of M9466 to our pipeline further supports our focus on synergistic approaches in oncology, with the potential for combination with tuvusertib as well as with multiple other modalities," said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck. "With our preclinical research programs in ADCs, DDR inhibitors, next-generation immuno-oncology compounds and oncogenic signaling assets, we are well-positioned to continue to fuel our clinical development efforts as we work to improve the futures of people touched by cancer."
Realizing the Full Potential of DNA Damage Response Inhibition
The company's leading pipeline of DDR inhibitors is being investigated across core hypotheses including synthetic lethality, activation of immune response, and synergy with cytotoxic drugs, to identify relevant combinations and understand which cancers are most likely to respond to different treatment regimens. Four investigational DDR inhibitor medicines in clinical trials include:
- Tuvusertib (M1774), a potentially best-in-class small-molecule oral inhibitor of the ataxia telangiectasia and Rad3-related (ATR) kinase;
- M9466, a next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) inhibitor, recently licensed from Jiangsu Hengrui Pharmaceuticals Co. Ltd. (Hengrui);
- Lartesertib (M4076), an ataxia telangiectasia mutated (ATM) kinase inhibitor; and
- Peposertib, a DNA-PK inhibitor.
Recently presented data lay the foundation for combination Phase II studies with tuvusertib. Data from DDRiver 301 Part B presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting show the ability to combine tuvusertib at a predicted efficacious dose with the PARP inhibitor niraparib, as well as encouraging activity in PARP-pretreated ovarian cancer. These findings complement data for the first-in-class tuvusertib and lartesertib combination first presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 in April. The company is exploring tuvusertib across three Phase II studies:
- Ongoing Phase Ib/II DDRiver NSCLC 322 study in combination with cemiplimab in ICI-resistant advanced non-small cell lung cancer (NSCLC) with biomarker stratification;
- Recently opened Phase II DDRiver EOC 302 study of tuvusertib plus lartesertib or niraparib in biomarker-selected PARP-resistant ovarian cancer; and
- Recently opened Phase II JAVELIN DDRiver Bladder study , in combination with BAVENCIO® (avelumab) in ICI-resistant advanced urothelial cancer.
For M9466 (also known as HRS-1167), data presented during the 2024 ASCO Annual Meeting from Hengrui's first-in-human clinical trial show a favorable safety profile and promising efficacy in PARP-naïve, PARP-sensitive tumors, supporting Merck's plans to further develop this investigational medicine in various combinations. The recently opened DDRiver 501 study will evaluate M9466 in combination with tuvusertib in solid tumors with relevant mutations and/or prior PARP inhibitor exposure, with a focus on castration-resistant prostate and ovarian cancers. The clinical development program will build on the company's expertise in genitourinary and gastrointestinal cancers and aims to expand the list of indications beyond the tumors shown to be sensitive to first-generation PARP inhibitors.
Driving Innovation in Antibody-Drug Conjugates
