Table 1. Active and pending clinical trials utilizing menin inhibitors†.
| Investigational agent | Clinical trial identification | Clinical trial phase | Patient population | Incorporation of chemotherapy |
|---|---|---|---|---|
| BMF-219 | NCT05153330 (COVALENT-101) | I | Adults‡ with relapsed/refractory AML, ALL, DLBCL, CLL/SLL, or multiple myeloma | No |
| BMF-219 | NCT05631574 (COVALENT-102) | I | Adults with KRAS-mutated non-small cell lung cancer, pancreatic cancer, colorectal cancer | No |
| BMF-219 | NCT05731544 (COVALENT-111) | I | Adults with type 2 diabetes mellitus | N/A |
| BMF-219 | NCT06152042 (COVALENT-112) | II | Adults aged 18–60 with type 1 diabetes mellitus | N/A |
| BN104 | NCT06052813 | I/II | Adults with relapsed/refractory AML with KMT2A or NPM1 alterations, relapsed ALL with KMT2A alterations | No |
| DSP-5336 | NCT04988555 | I/II | Adults with relapsed/refractory AML, ALL, or acute leukemia of ambiguous lineage. Need for KMT2A or NPM1 alterations varies by cohort | No |
| JNJ-75276617 | NCT04811560 | I | Adults with relapsed/refractory AML or ALL with KMT2A or NPM1 alterations | No |
| JNJ-75276617 | NCT05453903 | I | Adults with AML with KMT2A or NPM1 alterations | Azacitidine, venetoclax (arms A and B) |
| Cytarabine, daunorubicin or idarubicin (arm C) | ||||
| JNJ-75276617 | NCT05521087 | I | Patients less than 30 years with relapsed/refractory leukemia with KMT2A or NPM1 alterations | Fludarabine, cytarabine (AML) |
| Vincristine, dexamethasone, pegaspargase (ALL) | ||||
| KO-539 (ziftomenib) | NCT04067336 (KOMET-001) | I/II | Adults with relapsed/refractory AML with KMT2A or NPM1 alterations | No |
| KO-539 (ziftomenib) | NCT05735184 (KOMET-007) | I | Adults with relapsed/refractory AML with KMT2A or NPM1 alterations | Azacitidine, venetoclax, daunorubicin, cytarabine |
| KO-539 (ziftomenib) | NCT06001788 (KOMET-008) | I | Adults with relapsed/refractory AML with KMT2A or NPM1 alterations, including a FLT3 cohort | Fludarabine, cytarabine, idarubicin, gilteritinib (FLT3 cohort) |
| KO-539 (ziftomenib) | NCT05848687 (TINI 2) | I/II | Infants <1 year of age with KMT2A rearranged ALL, undifferentiated, or biphenotypic leukemia | Dexamethasone, mitoxantrone, pegaspargase, bortezomib, vorinostat, mercaptopurine, methotrexate, blinatumomab |
| SNDX-5613 (revumenib) | NCT04065399 (AUGMENT-101) | I/II | Patients with relapsed/refractory leukemia with KMT2A or NPM1 alterations | No |
| SNDX-5613 (revumenib) | NCT05326516 (AUGMENT-102) | I | Patients with relapsed/refractory leukemia with KMT2A or NPM1 alterations | Vincristine, prednisone, pegaspargase/calaspargase, daunorubicin, etoposide, cyclophosphamide (regimen 1) |
| Fludarabine, cytarabine (regimen 2) | ||||
| SNDX-5613 (revumenib) | NCT05360160 (SAVE) | I/II | Patients 12 years and older with relapsed/refractory AML or MPAL with myeloid phenotype | Decitabine/cedazuridine and venetoclax |
| SNDX-5613 (revumenib) | NCT05761171 (AALL2121) | II | Patients <6 years old with relapsed/refractory ALL, MPAL with KMT2A rearrangement with initial diagnosis <2 years old |
Vincristine, prednisone, calaspargase (regimen A) |
| Fludarabine, cytarabine (regimen B) | ||||
| SNDX-5613 (revumenib) | NCT05886049 | I | Adults with newly diagnosed AML with KMT2A or NPM1 alterations | Daunorubicin plus cytarabine |
| SNDX-5613 (revumenib) | NCT05731947 | I/II | Adults with progressive metastatic colorectal cancer (phase I) or solid tumors (phase II) | Phase II will compare SYDX-5613 response against trifluridine/tipiracil and regorafenib |
| SNDX-5613 (revumenib) | NCT06177067 | I | Patients 1–30 years old with relapsed/refractory AML with KMT2A, NPM1, and other eligible alterations | Azacitidine, venetoclax |
†, listed trials on clinicaltrials.gov using search terms “menin”, “revumenib”, and “ziftomenib” as of January 7, 2024; ‡, patient is 18 years of age or older. AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; DLBCL, diffuse large B-cell lymphoma; CLL, chronic lymphocytic lymphoma; SLL, small lymphocytic lymphoma; MPAL, mixed phenotype acute leukemia; KRAS, Ki-ras2, Kirsten rat sarcoma viral oncogene homolog; KMT2A, lysine methyltransferase 2A; NPM1, nucleophosmin 1; FLT3, FMS-related receptor tyrosine kinase 3.