Table 2.
Anti-CD47 Agents in Clinical Development. Abbreviations: AML, acute myeloid leukemia; aza, azacitidine; CMML, chronic myelomonocytic leukemia; F, fit for intensive chemotherapy; MDS, myelodysplastic syndrome; R/R relapsed or refractory; TN, treatment naïve; U, unfit for intensive chemotherapy; Ven, venetoclax. Note: * SIRPa targeting agent, all others target CD47. The following agents are in clinical development but AML patients not included in study: TG-1801, A0-176, TG1801 (anti-CD19 CD47 bispecific), IMC-002, STI-6643, SL-172154, ZL-1201, IMM01, & SRF231 (no longer in active development); PF-07257876 and IBI322 (anti-CD47 and PD-L1); IMM-0306 CD47xCD20 bispecific. SRF231 showed 90% receptor occupancy no complete or partial responses in solid tumor and lymphoma cohorts, development has been suspended. The following agents target SIRPa but AML patients are not included in study: GS-0189, CC-95251, BI765063/OSE-172.
| Agent | Phase | Enrollment | Status | Regimen | NCT | Population |
|---|---|---|---|---|---|---|
| Magrolimab (Hu5F9-G4) | III | 520 | Recruiting | Combination with aza | NCT04313881 | Treatment naïve (TN) higher risk MDS |
| Magrolimab (Hu5F9-G4) | III | 346 | Recruiting | Combination with aza | NCT04778397 |
TP53 mutated TN unfit (TNU) AML; TP53 mutated TN fit AML |
| Magrolimab (Hu5F9-G4) | Ib/II | 98 | Recruiting | Combination with ven/aza | NCT04435691 | Ib: Relapsed/Refractory (R/R) AML; II: TNU AML or TN < 75 years old with high risk cytogenetics +/− TP53 |
| Magrolimab (Hu5F9-G4) | Ib | 287 | Recruiting [105] | Combination with aza | NCT03248479 | R/R AML, TNU AML, RBC transfusion dependent low risk MDS |
| Magrolimab (Hu5F9-G4) | Ib | 13 | Completed | Combination with Atezolizumab | NCT03922477 | R/R AML |
| Magrolimab (Hu5F9-G4) | Ia | 20 | Completed [106] | Monotherapy | NCT02678338 | R/R AML; R/R higher risk MDS |
| TJ011133 (TJC4, Lemzoparlimab) | IIA | 80 | Recruiting | Combination with aza | NCT04202003 | TNU AML or TN higher risk MDS |
| TJ011133 (TJC4, Lemzoparlimab) | Ib | 120 | Recruiting | Combination with aza or ven/aza | NCT04912063 | TNU AML; high risk MDS |
| ALX148 (Evorpacept *) | I/II | 97 | Recruiting | Combination with ven/aza | NCT04755244 | R/R AML or new AML in patients ineligible for standard induction |
| AK117 | Ib/II | 160 | Recruiting | Combination with aza | NCT04980885 | AML, newly diagnosed or R/R |
| DSP107 * | Ib/II | 36 | Recruiting | Combination with aza | NCT04937166 | TNU AML, TN MDS, R/R MDS/CMML |
| TTI-621 | Ia/Ib | 260 | Recruiting | Monotherapy | NCT02663518 | R/R AML |
| TTI-662 | Ia/Ib | 150 | Recruiting | Ia: single agent 1b: combination with ven/aza |
NCT03530683 | TN TP53-mutated AML aza+TTI-662; TNU AML TTI-662 + aza/ven |
| IBI188 | Ia | 12 | Recruiting | Combination with aza | NCT04485065 | TN higher risk MDS |
| IBI188 | Ib | 126 | Recruiting | Combination with aza | NCT04485052 | R/R AML, TNU AML |
| CC-90002 | I | 28 | Terminated [107] | Monotherapy | NCT02641002 | R/R AML or high risk MDS |