Merck announces phase 3 trial initiations for four investigational candidates from its promising haematology and oncology pipeline

Merck, known as MSD outside of the United States and Canada, announced the initiation of pivotal phase 3 trials for four of its investigational candidates from its diverse pipeline in hematologic malignancies and solid tumours. Global phase 3 studies have been initiated and are actively enrolling for the following investigational candidates:

Bomedemstat, an investigational orally available lysine-specific demethylase 1 (LSD1) inhibitor, being evaluated for the treatment of certain patients with essential thrombocythemia (ET); Nemtabrutinib, an investigational oral, reversible, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, being evaluated for the treatment of certain patients with chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL); MK-2870, an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, which is being evaluated for certain patients with non-small cell lung cancer (NSCLC) and certain patients with previously treated endometrial carcinoma; and MK-5684, an investigational CYP11A1 inhibitor being developed in collaboration with Orion, which is being evaluated for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC).

“These phase 3 trial initiations for four of our investigational candidates represent a critical step forward in our efforts to advance potential treatment options for people with solid tumours and hematologic neoplasms and malignancies,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We have a proud legacy of turning breakthrough science into medicines that save and improve lives around the world, and we are dedicated to continuing research to expand our broad portfolio of oncology therapeutics to continue to address unmet needs in cancer care.”

Bomedemstat is an investigational orally available small molecule that inhibits LSD1, an enzyme that is potentially important for regulating the proliferation of hematopoietic stem cells and the maturation of progenitor cells. In non-clinical studies, bomedemstat demonstrated robust in vivo anti-tumour efficacy across a range of myeloid malignancies as a single agent and in combination with other therapeutic agents.

Merck has initiated the pivotal phase 3 randomized MK-3543-006 clinical trial (NCT06079879) evaluating bomedemstat compared to best available therapy (BAT) as treatment in patients with ET who have an inadequate response to or are intolerant of hydroxyurea. Global recruitment of the trial has begun, with patients now enrolling.

MK-3543-006 is a phase 3, global, randomized, open-label, active-comparator-controlled clinical study that is slated to enroll approximately 300 patients around the world. The primary endpoint of the study is durable clinicohematologic response (DCHR) rate, and key secondary endpoints include duration of clinicohematologic response (DOCHR), duration of hematologic remission (DOHR), disease progression rate and event free survival (EFS).

Bomedemstat has US Food and Drug Administration (FDA) Orphan Drug and Fast Track Designation for the treatment of ET and myelofibrosis (MF), Orphan Drug Designation for the treatment of acute myeloid leukaemia (AML) and Priority Medicines (PRIME) scheme designation by the European Medicines Agency (EMA) for the treatment of MF. Merck presented updated data from the Phase 2b MK-3543-003 trial, including first time genomic data, at the American Society for Haematology (ASH) Annual Meeting in December 2023. This is one of multiple phase 2 clinical trials where bomedemstat is currently being evaluated alone and in combination for the treatment of myeloproliferative neoplasms (MPNs) such as ET, MF and polycythemia vera (PV).

Nemtabrutinib is an investigational oral, reversible, non-covalent BTK inhibitor that suppresses oncogenic B-cell receptor signalling with activity against wild-type BTK and BTK pathway mutants. Nemtabrutinib aims to address a common mechanism of resistance with currently available irreversible, covalent BTK inhibitors by binding in an alternative way to the BTK protein.

Merck has initiated the pivotal phase 3 randomized BELLWAVE-011 clinical trial (NCT06136559) evaluating nemtabrutinib versus investigator's choice of ibrutinib or acalabrutinib in patients with previously untreated CLL and SLL. Global recruitment of the trial has begun, with patients now enrolling.

BELLWAVE-011 is a phase 3, global, randomized, open-label, active-comparator-controlled clinical study that is slated to enroll approximately 1,200 patients around the world. The primary endpoints of the study are objective response rate (ORR) per Chronic Lymphocytic Leukaemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR) and progression-free survival (PFS) per iwCLL Criteria 2018 as assessed by BICR. Key secondary endpoints include overall survival (OS) and duration of response (DOR) per iwCLL Criteria 2018 as assessed by BICR.

Merck is committed to research with nemtabrutinib across B-cell malignancies and is establishing a robust program of clinical trials under the name BELLWAVE. In addition to BELLWAVE-011, a phase 3 study is currently underway in patients with previously untreated CLL and SLL without TP53 aberrations (BELLWAVE-008, NCT05624554).

MK-2870 is an investigational ADC that consists of an antibody targeting TROP2 linked to a belotecan-derived payload. TROP2 is highly expressed in a variety of epithelial-derived tumours and can promote tumour cell proliferation, invasion and metastasis. TROP2 ADCs specifically target TROP2-expressing tumour cells to deliver cytotoxic effects and have shown encouraging anti-tumour activity in clinical studies.

Merck has initiated three pivotal phase 3 clinical trials evaluating MK-2870 in which patients are now enrolling: MK-2870-004 (NCT06074588), MK-2870-007 (NCT06170788) and MK-2870-005 (NCT06132958).

MK-2870-004 is a phase 3, global, randomized, open-label, active-comparator-controlled clinical study evaluating MK-2870 compared to chemotherapy (docetaxel or pemetrexed) for the treatment of previously treated advanced or metastatic NSCLC with EGFR mutations or other genomic alterations. The trial is slated to enroll approximately 556 patients around the world. The primary endpoints of the study are PFS and OS, and key secondary endpoints include ORR and DOR.

MK-2870-007 is a phase 3, global, randomized, open-label, active-comparator-controlled clinical study evaluating MK-2870 in combination with Keytruda (pembrolizumab) compared to Keytruda alone in patients with metastatic NSCLC with a PD-L1 tumour proportion score (TPS) =50%. The trial is slated to enroll approximately 614 patients around the world. The primary endpoint of the study is OS, and key secondary endpoints include PFS, DOR and objective response (OR).

MK-2870-005 is a phase 3, global, randomized, open-label, active-comparator-controlled clinical study evaluating MK-2870 compared to a treatment of physicians’ choice in patients with endometrial carcinoma who have received prior platinum-based chemotherapy and immunotherapy. The trial is slated to enroll approximately 710 patients around the world. The primary endpoints of the study are PFS per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by BICR and OS. Key secondary endpoints include ORR per RECIST 1.1 as assessed by BICR and DOR per RECIST 1.1 as assessed by BICR.

MK-2870 was developed by Kelun-Biotech. Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. Under a collaboration agreement, Kelun-Biotech has granted Merck the exclusive rights to develop, manufacture, and commercialize MK-2870 in all territories outside of Greater China. In addition to MK-2870-004, MK-2870-007 and MK-2870-005, Merck intends to rapidly advance the global clinical development program evaluating MK-2870 as a monotherapy and in combination with Keytruda in various solid tumours.

MK-5684 is an oral, non-steroidal and selective inhibitor of the CYP11A1 enzyme discovered and developed by Orion and is being investigated for the treatment of hormone-dependent cancers, such as prostate cancer. By inhibiting CYP11A1 enzyme activity, MK-5684 is designed to suppress the production of all steroid hormones and their precursors that may activate the androgen receptor signalling pathway.

Merck and Orion Corporation have initiated two pivotal Phase 3 clinical trials evaluating MK-5684 (ODM-208) in combination with hormone replacement therapy (HRT), for the treatment of certain patients with mCRPC. Patients are now enrolling in these two trials, named OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650).

OMAHA1 is a randomized, open-label Phase 3 trial evaluating MK-5684 in combination with HRT for the treatment of patients with later-line mCRPC who have failed one prior new hormonal agent (NHA) and one or two prior taxanes compared to an alternative NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,200 patients around the world. The primary endpoints are OS and radiographic progression-free survival (rPFS) by androgen receptor ligand-binding domain (AR LBD) mutation status. Secondary endpoints include time to first subsequent therapy (TFST), ORR and DOR.

OMAHA2a is a randomized, open-label Phase 3 trial evaluating MK-5684 in combination with HRT for the treatment of patients with front-line mCRPC who have failed one prior NHA compared to physician’s choice of NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,500 patients around the world. The primary endpoints are OS and rPFS by AR LBD mutation status. Secondary endpoints include TFST, ORR and DOR.

Orion is a globally operating Finnish pharmaceutical company that develops, manufactures and markets human and veterinary pharmaceuticals and active pharmaceutical ingredients. The core therapy areas of their pharmaceutical R&D are oncology and pain.

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!