TABLE 1.
Ongoing clinical trials of targeted agents.
| Target | Drug | Trial phase | Patient population | Single agent/combination | Preliminary results (if available) | Ref/identifier | Status |
| MDM2 | Idasanutlin (RG7388; RO5503781) | IB/II | 60+ years old with R/R or secondary AML not eligible for cytotoxic therapy | Combination with venetoclax | NCT02670044 | Recruiting | |
| III | R/R AML | Combination with cytarabine | NCT02545283 | Recruiting | |||
| IB/II | Newly diagnosed AML | Combination with cytarabine and daunorubicin for induction; combination with cytarabine for consolidation; single agent for maintenance of CR1 | NCT03850535 | Recruiting | |||
| AMG 232 | IB | R/R or newly diagnosed AML with WT TP53 | Combination with decitabine | NCT03041688 | Recruiting | ||
| HDM201 | I/II | R/R or newly diagnosed AML | Combination with cytarabine, anthracyclines, midostaurin | NCT03760445 | Recruiting | ||
| IB | R/R or newly diagnosed AML unfit for standard induction with WT TP53, or high-risk MDS who have failed HMAs | Combination with MBG453 or venetoclax | NCT03940352 | Recruiting | |||
| Milademetan (DS-3032b) | I | R/R AML | Monotherapy | NCT03671564 | Active, not recruiting | ||
| I/II | R/R AML, WT TP53 | Combination with low-dose cytarabine | NCT03634228 | Recruiting | |||
| I | R/R AML with WT TP53, or high-risk MDS | Alone and in combination with azacitidine | NCT02319369 | Recruiting | |||
| I | R/R or newly diagnosed AML unfit for standard induction with FLT3-ITD mutation | Combination with quizartinib | NCT03552029 | Recruiting | |||
| ALRN-6924 | I | R/R AML with WT TP53 | Alone and in combination with cytarabine | 18 patients; no DLTs, only grade 3+ treatment-related AE was thrombocytopenia; 1 patient in combination arm with >50% reduction in blasts | NCT02909972 (Lambert et al., 2019) | Active, not recruiting | |
| p53 | APR-246 | IB/II | AML with WBC <20K, MDS, MDS/MPN, CMML, with TP53 mutation | Combination with azacitidine | NCT03588078 | Active, not recruiting | |
| II | AML or MDS with TP53 mutation | Combination with azacitidine as maintenance following allo SCT and achievement of CR | NCT03931291 | Recruiting | |||
| IB/II | AML (20–30% blasts), MDS, MDS/MPN, CMML, with TP53 mutation | Combination with azacitidine | NCT03072043 | Active, not recruiting | |||
| Selinexor (KPT-330) | II | Newly diagnosed AML, 60 years and older | Combination with cytarabine and daunorubicin for induction, with cytarabine for consolidation, and monotherapy for maintenance | NCT02835222 | Recruiting | ||
| IB | R/R AML or DLBCL | Combination with venetoclax | NCT03955783 | Recruiting | |||
| I | AML and high-risk MDS after allo-SCT | Monotherapy to eliminate MRD and maintain remission | NCT02485535 | Active, not recruiting | |||
| I | R/R AML | Combination with FLAG-Ida | NCT03661515 | Recruiting | |||
| Arsenic trioxide | II | AML with TP53 mutation | Combination with decitabine and cytarabine | NCT03381781 | Not yet recruiting | ||
| Aurora kinase | AZD2811 | I/II | Newly diagnosed AML not eligible for intensive induction, or R/R AML | Alone or in combination with azacitidine | NCT03217838 | Recruiting | |
| PLK | Onvansertib (PCM-075) | I/II | R/R AML | Combination with LDAC or decitabine | 21 patients. No serious treatment-related AEs at the first 3 doses. Responses in 5 of 19 evaluable pts (2 CRc, 1 PR, and 2 MLFS). Greatest response in the onvansertib and decitabine arm with 2/4 patients achieving CRc. | NCT03303339 (Dennis et al., 2012) | Recruiting |
| CFI-400945 | I | R/R AML or MDS | Monotherapy | NCT03187288 | Recruiting | ||
| DOT1L | Pinometostat (EPZ-5676) | IB/II | Newly diagnosed AML with MLL rearrangement | Combination with cytarabine and daunorubicin induction | NCT03724084 | Recruiting | |
| IB/II | Newly diagnosed or R/R AML with MLL rearrangement | Combination with azacitidine | NCT03701295 | Recruiting | |||
| IL-3 receptor alpha (CD123) | SL-401 | I/II | AML in CR; any MRD status for stage 1 and MRD+ for stage 2 | Monotherapy | 9 patients in Stage 1 and 7 patients in Stage 2. No DLTs; most common grade 3+ treatment-related AEs were transaminitis and thrombocytopenia; two with grade 3 capillary leak syndrome. MRD and DFS analysis for Stage 2 is ongoing | NCT02270463 (Dohner et al., 2014b) | Active, not recruiting |
| I/II | Newly diagnosed treatment-related or secondary AML, R/R AML, and blastic plasmacytoid dendritic cell neoplasm (BPDCN) | Monotherapy | Results published for BPDCN but not AML | NCT02113982 | Active, not recruiting | ||
| I | Newly diagnosed AML not eligible for intensive induction, R/R AML, High-risk MDS. CD123 expression confirmed | Combination with azacitidine | NCT03113643 | Recruiting | |||
| Bromodomain | Mivebresib (ABBV-075) | I | R/R AML, as well as other solid or hematologic malignancies that are refractory or for which standard of care does not exist | Alone and in combination with venetoclax | 41 patients (19 monotherapy and 22 combination). No DLTs; common grade 3+ AEs of cytopenias. Only efficacy data reported so far is median best percentage BM blast change for 26 evaluable pts which was −20% (range −98% to +300%) | NCT02391480 (Nguyen et al., 2011) | Completed |
| GSK525762 | I/II | R/R AML or those older than 65 not candidates for/refused standard chemotherapy | Monotherapy | 46 pts. DLTs included diarrhea and decreased EF. Common grade 3+ AEs were diarrhea, febrile neutropenia, thrombocytopenia, hyperglycemia, and fatigue. 2 CRcs and 3 PRs. Most responses were delayed and required at least 10 weeks of therapy to manifest | NCT01943851 (Bernt et al., 2011) | Recruiting | |
| RO6870810/ TEN-010 | I | R/R AML and MDS | Monotherapy | Not yet published | NCT02308761 | Completed | |
| FT-1101 | I/IB | AML, MDS, NHL that is R/R or for whom standard treatment are contraindicated | Alone and in combination with azacitidine | Not yet published | NCT02543879 | Completed | |
| ABBV-744 | I | R/R AML and metastatic castrate-resistant prostate cancer | Monotherapy | NCT03360006 | Recruiting | ||
| PLX51107 | I | AML and MDS | Combination with azacitidine | NCT04022785 | Not yet recruiting | ||
| CTLA-4 | Ipilimumab | I | Intermediate-II, high-risk, or any FLT3+ AML; IPSS intermediate-2 or high-risk MDS | Allogeneic HSCT followed by ipilimumab, ipilimumab + nivolumab, or nivolumab. | NCT02846376 | Recruiting | |
| I | R/R AML or MDS following allogeneic HSCT | Allogeneic HSCT followed by ipilimumab, ipilimumab + nivolumab, or nivolumab | NCT03600155 | Recruiting | |||
| I | R/R AML or newly diagnosed AML 75 years or older; R/R MDS. | Combination with decitabine. | NCT02890329 | Recruiting | |||
| II | R/R AML, newly diagnosed AML age 65+ unfit for/decline standard induction, or newly diagnosed secondary AML | Azacitidine and nivolumab ± ipilimumab. | NCT02397720 | Recruiting | |||
| MCL-1 | AMG 176 | I | R/R AML or MM | Alone and in combination with azacitidine (AML) and carfilzomib (MM) | NCT02675452 | Active, not recruiting | |
| AMG 397 | I | R/R AML, MM, NHL | Monotherapy. | NCT03465540 | Active, not recruiting | ||
| S64315 | I | R/R AML, or AML secondary to MDS treated at least with HMA, or untreated AML if >65 and not candidate for intensive/alternative chemotherapy; R/R MDS. | Monotherapy | NCT02979366 | Recruiting | ||
| IB | R/R AML, or AML secondary to MDS treated at least with HMA and without established alternative therapy, or untreated AML if >65 and not candidate for intensive/alternative chemotherapy | Combination with venetoclax | NCT03672695 | Recruiting | |||
| AZD5991 | I/II | R/R AML as well as other R/R hematologic malignancies; must have received at least 2 prior lines of therapy | Alone and in combination with venetoclax | NCT03218683 | Recruiting | ||
| CD47 | Magrolimab (Hu5F9-G4; 5F9) | IB | Newly diagnosed AML not eligible for intensive induction, or untreated intermediate to very high risk MDS | Alone and in combination with azacitidine | 22 pts with AML. Common treatment-related AEs were cytopenias. No MTD reached. ORR 64% (14/22), CR 41%, CRi 14%, PR 5%, MLFS 5%. MRD negativity noted in 57% of responders | NCT03248479 (Glaser et al., 2012) | Recruiting |
| IB | R/R AML | Combination with atezolizumab | NCT03922477 | Recruiting | |||
| TTI-621 (SIRPaFc) | IA/IB | R/R hematologic malignancies and selected solid tumors | Monotherapy | NCT02663518 | Recruiting |
Allogeneic HSCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; CR, complete response; MDS, myelodysplastic syndrome; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; ORR, overall response rate; PR, partial response; R/R, relapsed/refractory.