Merck Launches Pivotal Phase III Trials of Novel Drugs for Oncologic, Hematologic Malignancies

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Merck’s robust oncology and hematology pipeline continues to advance with the launch of pivotal Phase III trials for four novel candidates for hematologic malignancies and solid tumors. The company announced active enrollment for investigational drugs that treat essential thrombocythemia (ET); chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL); non-small cell lung cancer (NSCLC); certain patients with previously treated endometrial carcinoma; and metastatic castration-resistant prostate cancer (mCRPC).

“These Phase III 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 tumors and hematologic neoplasms and malignancies,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a press release. “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 for ET

The pivotal randomized MK-3543-006 clinical trial (NCT06079879) will analyze bomedemstat vs. best available therapy (BAT) for the treatment of patients with ET who have an inadequate response to, or are intolerant of, hydroxyurea. The investigational orally-available small molecule inhibits LSD1, which may help to regulate the proliferation of hematopoietic stem cells and the maturation of progenitor cells, according to Merck. Bomedemstat was found to produce robust in vivo anti-tumor efficacy across a range of myeloid malignancies both as a single agent and combined with other therapeutic agents in non-clinical studies, according to Merck.

Bomedemstat was previously granted FDA Orphan Drug and Fast Track designations for ET and myelofibrosis (MF) and Orphan Drug Designation for acute myeloid leukemia (AML).

Nemtabrutinib for CLL and SLL

The pivotal, randomized, open-label, active-comparator-controlled BELLWAVE-011 clinical trial (NCT06136559) is analyzing nemtabrutinib compared with investigator's choice of ibrutinib or acalabrutinib in patients with previously untreated CLL and SLL. The investigational oral, reversible, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor has been shown to suppress oncogenic B-cell receptor signaling with activity against wild-type BTK and BTK pathway mutants.

BELLWAVE-011 is set to enroll approximately 1,200 patients around the world with primary endpoints of objective response rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR) and progression-free survival (PFS) per iwCLL Criteria 2018 as assessed by BICR, overall survival (OS) and duration of response (DOR) per iwCLL Criteria 2018 as assessed by BICR.

Nemtabrutinib is also being evaluated in the Phase III BELLWAVE-008 (NCT05624554) trial in patients with previously untreated CLL and SLL without TP53 aberrations.

MK-2870 for NSCLC and Endometrial Carcinoma

MK-2870 is an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) Merck developed in collaboration with Kelun-Biotech. The ADC is being evaluated in the pivotal Phase III clinical trials MK-2870-004 (NCT06074588), MK-2870-007 (NCT06170788), and MK-2870-005 (NCT06132958).

The global, randomized, open-label, active-comparator-controlled MK-2870-004 trial will analyze MK-2870 vs. chemotherapy with docetaxel or pemetrexed in patients with previously treated advanced or metastatic NSCLC with EGFR mutations or other genomic alterations. Investigators will enroll approximately 556 patients worldwide for the trial, which has primary endpoints of PFS and OS, with key secondary endpoints that include ORR and DOR.

The global, randomized, open-label, active-comparator-controlled MK-2870-007 clinical trial will evaluate MK-2870 in combination with Keytruda (pembrolizumab) compared to Keytruda monotherapy in patients with metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. The trial will enroll approximately 614 patients worldwide, with the primary endpoint of OS, and key secondary endpoints that include PFS, DOR and objective response (OR).

The global, randomized, open-label, active-comparator-controlled MK-2870-005 clinical trial will analyze MK-2870 vs. physicians’ choice of treatment among patients with endometrial carcinoma who have received prior platinum-based chemotherapy and immunotherapy. The trial will enroll approximately 710 patients worldwide, with the primary endpoints of PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by BICR and OS, and key secondary endpoints that include ORR per RECIST 1.1 as assessed by BICR and DOR per RECIST 1.1 as assessed by BICR.

MK-5684 for mCRPC

MK-5684 is an oral, non-steroidal and selective CYP11A1 inhibitor developed in collaboration with Orion under evaluation for the treatment of hormone-dependent cancers in the OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650) clinical trials.

The randomized, open-label OMAHA1 trial is analyzing MK-5684 in combination with hormone replacement therapy (HRT) for patients with later-line mCRPC who failed a prior new hormonal agent (NHA) and one or two prior taxanes compared to an alternative NHA (abiraterone or enzalutamide). OMAHA1 will enroll approximately 1,200 patients worldwide with primary endpoints of OS and radiographic PFS (rPFS) by androgen receptor ligand-binding domain (AR LBD) mutation status and secondary endpoints that include time to first subsequent therapy (TFST), ORR, and DOR.

The randomized, open-label OMAHA2a trial is analyzing MK-5684 in combination with HRT for patients with front-line mCRPC who failed a prior NHA compared to physician’s choice of NHA (abiraterone or enzalutamide). OMAHA2a will enroll approximately 1,500 patients worldwide, with primary endpoints of OS and rPFS by AR LBD mutation status and secondary endpoints that include TFST, ORR, and DOR.

Reference

Merck Announces Phase 3 Trial Initiations for Four Investigational Candidates From its Promising Hematology and Oncology Pipeline. Merck. News release. January 5, 2024. https://www.merck.com/news/merck-announces-phase-3-trial-initiations-for-four-investigational-candidates-from-its-promising-hematology-and-oncology-pipeline/