Global Phase 3 studies started for bomedemstat (LSD1 inhibitor), nemtabrutinib (BTK inhibitor), MK-2870 (anti-TROP2 ADC) and MK-5684 (CYP11A1 inhibitor)
Comprehensive clinical development programs being initiated for each investigational candidate
Demonstrates company’s commitment to research across novel mechanisms of action in hematologic neoplasms/malignancies, as well as lung, endometrial and prostate cancers
RAHWAY, NJ, USA I January 05, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of pivotal Phase 3 trials for four of its investigational candidates from its diverse pipeline in hematologic malignancies and solid tumors. 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 leukemia (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 tumors 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.”
About Bomedemstat and MK-3543-006
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-tumor 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 U.S. 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 leukemia (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 Hematology (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).
About Nemtabrutinib and BELLWAVE-011
Nemtabrutinib is an investigational oral, reversible, non-covalent BTK inhibitor that suppresses oncogenic B-cell receptor signaling 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 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. 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).
About MK-2870 and MK-2870-004, MK-2870-007 and MK-2870-005
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 tumors and can promote tumor cell proliferation, invasion and metastasis. TROP2 ADCs specifically target TROP2-expressing tumor cells to deliver cytotoxic effects and have shown encouraging anti-tumor 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 tumor 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 Tumors (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 tumors.
About MK-5684 (ODM-208) and OMAHA1 and OMAHA2a
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 signaling 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
About Merck in hematology
Merck is committed to advancing innovation and care for people with blood cancers. Today, the company is focused on advancing its approved medicines and conducting a wide-ranging clinical development program with the aim of addressing evolving unmet needs in hematologic oncology. Among Merck’s research efforts are studies evaluating KEYTRUDA, coformulations of novel checkpoint inhibitors with KEYTRUDA and two investigational medicines as monotherapy or in combination in a range of blood cancers, including CLL and B-cell lymphomas.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
