Table 2.
Advancements of NK cell activation immune checkpoint inhibitor for hematologic and solid tumors
| Type of therapy | NK cell activation via immune checkpoint inhibitors | |||
|---|---|---|---|---|
| Authors (reference) | Porcu [7] | Browning [8] | Yang [9] | Timmerman [10] |
| Trial identifier (Phase) | NCT03902184 (II) | NCT05002816 (I/II) | NCT05805943 (I) | NCT03598608 (I/II) |
| Agents | Lacutamab, an ICI of KIR3DL2 | Elotuzumab(an ICI of SLAMF7) + belantamab mafodotin | IMM0306, a fusion protein of CD20 with the CD47 binding domain of SIRPa | Favezelimab (anti–LAG-3 monoclonal antibody) + pembrolizumab (a PD-1 inhibitor) |
| Malignancy | R/R mycosis fungoides | R/R MM | R/R CD20-positive B-cell non-Hodgkin’s lymphoma | R/R classical Hodgkin lymphoma |
| Patient number | 107 | 12 | 48 | 30 |
| Male | N/A | N/A | 30% | N/A |
| Median Age and (or) range (years) | 62 | 66.5 (59–79) | 56 | N/A |
| Clinical trial design | Lacutamab 750 mg was administered as an IV infusion until disease progression or unacceptable toxicity | Elotuzumab 10 mg/kg IV on days 1, 8, 15, 22 every 28 days for cycles 1 and 2; followed by 20 mg/kg on day 1 of each 28-day cycle. Belantamab mafodotin IV with the starting dose of 1.9 mg/kg IV at every 4-week interval | IMM0306 was administered at escalating doses of 0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg IV once a week until disease progression or intolerable toxicity | Pembrolizumab 200 mg IV Q3W plus favezelimab 200 mg starting dose, then dose escalation to 800 mg IV Q3W; and a dose expansion phase (pembrolizumab 200 mg Q3W plus favezelimab 800 mg Q3W for up to 35 cycles) |
| Median Follow-up (months) | 11.8 | N/A | N/A | 36.9 |
| Response rate | ORR 22.4% | PR 40% | ORR 30.3% | ORR 83% |
| Survival | Median PFS 10.2 months | N/A | Median PFS 10.58 months | Median PFS 19.4 months, 24-month OS rate 93% |
| Summary | It confirms promising clinical activity of lacutamab, with a favorable safety and tolerability profile | The combination indicates an encouraging safety profile and a promising preliminary efficacy in those patients | IMM0306 is well-tolerated and with promising preliminary anti-tumor activity especially in patients with R/R FL and MZL | It demonstrates sustained antitumor activity and manageable safety in patients studied |
CPI checkpoint inhibitors, FL follicular lymphoma, IV intravenously, KIR3DL2 Killer cell immunoglobulin like receptor 3DL2, MM multiple myeloma, MZL: marginal zone lymphoma, N/A not available, NK Natural killer, ORR objective response rate, PFS: progression-free survival, PR partial response, Q4W once every 4 weeks, Q3W once every 3 weeks, R/R relapsed or refractory