Table 1. CoREST complex–targeting molecules now in clinical development.
Clinical trials investigating CoREST complex–targeting molecules are summarized, highlighting their indications, efficacy, trial phases, and the most common treatment-emergent adverse events. GVHD, graft-versus-host disease; CSF, colony-stimulating factor.
| Trial number | Status | CoREST complex–targeting molecules | Combination treatment | Indications | Phase | Efficacy | Most common treatment-emergent adverse events |
|---|---|---|---|---|---|---|---|
| NCT04081220 | Recruiting | Bomedemstat (IMG-7289)* | Essential thrombocythemia | 2 | |||
| NCT05558696 | Recruiting | Polycythemia vera | 2 | ||||
| NCT05597306 | Recruiting | Venetoclax | AML | 1 | |||
| NCT05569538 | Recruiting | Myelofibrosis | 2 | ||||
| NCT02842827 | Completed (245) | Tretinoin | AML, MDS | 1|2 | Overall response rate of 28.2% in AML | Diarrhea (42%), nausea (42%), and thrombocytopenia (38%) | |
| NCT04262141 | Recruiting | Essential thrombocythemia|polycythemia vera | 2 | ||||
| NCT04254978 | Completed (213) | Essential thrombocythemia | 2 | 95% had reduced platelet counts to ≤400 × 109/liter in a median of 10 weeks | Dysgeusia (55%), constipation (38%), thrombocytopenia (34%), and arthralgia (27%) | ||
| NCT03136185 | Completed (246, 247) | Myelofibrosis | 1|2 | 72% had a reduction in the total symptom score, 64% had a reduction in the spleen volume from the baseline | Dysgeusia (36%), diarrhea (34%), thrombocytopenia (29%), and anemia (22%) | ||
| NCT05191797 | Recruiting | Atezolizumab | Extensive-stage SCLC|limited-stage SCLC | 1|2 | |||
| NCT04748848 | Terminated (no results posted) | CC-90011* | Venetoclax, azacitidine | AML | 1 | ||
| NCT04350463 | Completed (216) | Nivolumab | SCLC or squamous NSCLC | 2 | Overall response rate of 5.7–10.3% | Anemia (51.1%), thrombocytopenia (46.6%), decreased appetite (29.5%), and asthenia (26.1%) | |
| NCT04628988 | Completed (no results posted) | Prostatic neoplasms | 1 | ||||
| NCT02875223 | Terminated (215) | Lymphoma, non-Hodgkin neoplasms | 1 | Overall response rate of 4% | Fatigue (48%) and thrombocytopenia (46%) | ||
| NCT02034123 | Terminated (219) | GSK2879552* | SCLC | 1 | Poor disease control. Unfavorable risk-to-benefit ratio | Thrombocytopenia (41%). 14% of patients developed encephalopathy leading to one death and study termination. | |
| NCT02177812 | Terminated (218) | Tretinoin | AML | 1 | Unfavorable risk-to-benefit ratio | Febrile neutropenia (54%), nausea (46%), hypokalemia (41%), and thrombocytopenia (20%) | |
| NCT05546580 | Recruiting | Iadademstat (ORY-1001)* | Gilteritinib | AML | 1 | ||
| NCT05420636 | Recruiting | Paclitaxel | SCLC | 2 | |||
| NCT06287775 | Recruiting | Atezolizumab or durvalumab | Extensive-stage SCLC | 1|2 | |||
| NCT03132324 | Terminated | INCB059872* | Sickle cell disease | 1 | Terminated due to business decisions | ||
| NCT03514407 | Terminated | Relapsed Ewing sarcoma | 1 | ||||
| NCT02959437 | Terminated | Pembrolizumab and epacadostat | Solid tumors|advanced malignancies|metastatic cancer | 1|2 | |||
| NCT02712905 | Terminated | Azacitadine and tretinoin | Solid tumors and hematologic malignancy | 1|2 | |||
| NCT05268666 | Recruiting | JBI-802* | Locally advanced solid tumor|metastatic solid tumor | 1|2 | |||
| NCT03505528 | Completed (248) | Phenelzine sulfate* | Paclitaxel | Metastatic breast cancer | 1 | Dizziness (7%), fatigue (5%), neutropenia (3%), and peripheral neuropathy (3%) | |
| NCT04611139 | Withdrawn | Seclidemstat (SP-2577)* | Pembrolizumab | Gynecologic cancers | 1 | ||
| NCT05266196 | Enrolling_by_invitation | Ewing or Ewing-related sarcomas | 1|2 | ||||
| NCT03600649 | Active_not_recruiting | Topotecan and cyclophosphamide | Ewing or Ewing-related sarcomas | 1 | |||
| NCT04734990 | Recruiting | Azacitidine | MDS or chronic myelomonocytic leukemia | 1|2 | |||
| NCT03895684 | Completed (249) | Advanced solid tumors | 1 | 54% had the best response of stable disease with a median time to progression of 4.3 months | Diarrhea (5.3%) and abdominal pain (5.3%) | ||
| NCT03228433 | Terminated (228) | TAK-418* | Healthy volunteers | 1 | Headache (50%), nausea (22%), and decreased appetite (17%) | ||
| NCT03501069 | |||||||
| NCT02273102 | Completed (250) | TCP* | Tretinoin | AML | 1 | Overall response rate of 23.5% (in combination with ATRA) | Fatigue (35%), creatinine increased (29%), dizziness (29%), dry mouth (29%), and headache (29%) |
| NCT02261779 | Terminated (229) | Tretinoin | AML | 1|2 | Refractory/progressive disease and infectious complications led to termination | Vertigo (39%) and hypotension (22%) | |
| NCT02717884 | Unknown (251) | Tretinoin low-dose cytarabine | AML, MDS | 1|2 | Partial remission (8%) | Thrombocytopenia (45.8%) and neutropenia (20.8%) | |
| NCT05887492 | Recruiting | TNG260† | Pembrolizumab | STK11-mutated solid tumors | 1|2 | ||
| NCT04594031 | Withdrawn | UM171‡ | Sickle cell disease|umbilical cord blood|hematopoietic cell proliferation | 1 | |||
| NCT03913026 | Active_not_recruiting | High-risk hematologic malignancy|cord blood transplant | 2 | ||||
| NCT03441958 | Active_not_recruiting | Multiple myeloma | 1|2 | ||||
| NCT04990323 | Recruiting | High-risk myeloid malignancies|cord blood transplant | 1|2 | ||||
| NCT04103879 | Active_not_recruiting | High-risk hematological malignancy|cord blood transplant | 2 | ||||
| NCT02668315 | Completed (233, 236) | Hematologic malignancy | 1|2 | Probability of nonrelapse mortality: 4.5% (UM171) versus 30% (unmanipulated cord blood); probability of GVHD-free, relapse-free survival: 63.6% (UM171) versus 27.9% (unmanipulated cord blood) | Grade 3 febrile neutropenia (73%) and bacteremia (41%) | ||
| NCT04932291 | Completed (252) | Vafidemstat (ORY-2001)* | Borderline personality disorder | 2 | 58.6% reduction in the STAXI-2 Trait Anger scale (agitation and aggression) | Headache (12.3%), nasopharyngitis (8.5%), and reduced platelet counts (7.5%) | |
| NCT03867253 | Completed (232) | Mild to moderate Alzheimer’s disease | 2 | Reduction of proinflammatory YKL40 and NFL levels in CSF. Substantial reduction in agitation-aggression after 12-month treatment. | Safe and well tolerated. Specific safety data are not posted. |
*LSD1 inhibitor.
†HDAC1 inhibitor.
‡CoREST complex degrader.