Table 2.
Relevant clinical data of immunotherapy agents with potential effect on NK cells. Legend -> AE: adverse event; CI: confidence interval; CBR: clinical benefit rate; HR: hazard ratio; ITT: intent-to-treat; MTD: maximum-tolerated dose; NR: not reached; NSCLC: non-small cell lung cancer; ORR: objective response rate; RCC: renal cell carcinoma; SAE: severe adverse events. * p values were not reported in the interim analysis.
| Target | Agent | Study | Population | Regimens | Outcomes |
|---|---|---|---|---|---|
| SLAM7 | Elotuzumab | Yashar et al. (single-arm phase II trial) [76] |
13 patients with high-risk relapsed/refractory multiple myeloma | Elotuzumab plus pomalidomide, carfilzomib, and low-dose dexamethasone | ORR: 45.4%; CBR: 54.5% SAE rate: 31% |
| TIGIT | Tiragolumab | CITYSCAPE (open-label, randomized, phase II trial) [70] |
135 patients with advanced NSCLC (PD-L1 ≥ 1%) | Tiragolumab plus atezolizumab vs. atezolizumab alone |
INTERIM ANALYSIS * ITT population Median PFS: 5.6 vs. 3.9 months; HR: 0.62 (95% CI: 0.42–0.91) Median OS: 23.2 vs. 14.5 months; HR: 0.69 (95% CI: 0.44–1.07) PD-L1 ≥ 50% Median PFS: 16.6 vs. 4.1 months; HR: 0.29 (95% CI: 0.15–0.53) Median OS: NR vs. 12.8 months; HR: 0.23 (95% CI: 0.10–0.53) PD-L1 between 1–49% Median PFS: 4.0 vs. 3.6 months; HR: 1.07 (95% CI: 0.67–1.71) Median OS: 13.3 vs. 14.5 months; HR: 1.16 (95% CI: 0.70–1.94) |
| IDO1 | Epacadostat | ECHO-110 (phase Ib trial) [77] |
29 patients with advanced, pre-treated NSCLC | Epacadostat (increasing doses) plus atezolizumab | Grade ≥ 3 AEs rate: 24% 8 patients achieved stable disease 1 patient achieved partial response |
| ECHO-202/KEYNOTE-037 (phase I/II trial) [78] |
62 patients with advanced solid tumors | Epacadostat (increasing doses) plus pembrolizumab | Grade ≥ 3 AEs rate: 24% ORR melanoma: 12/22 patients (55%) ORR NSCLC: 5/12 patients (42%) ORR RCC: 2/11 patients (18%) |
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| ECHO-301/KEYNOTE-252 (placebo-controlled, randomized, phase III trial) [79] |
706 patients with unresectable stage III or IV melanoma previously untreated with PD-1 or PD-L1 checkpoint inhibitors | Epacadostat plus pembrolizumab vs. placebo plus pembrolizumab | Median PFS: 4.7 vs. 4.9 months; HR: 1.00 (95% CI: 0.83–1.21; p = 0.52) Median OS: not reached in any arm; HR: 1.13 (95% CI: 0.86–1.49; p = 0.81) |
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| LAG-3 | Relatlimab | Ascierto et al. (phase I/IIa trial) [72] |
43 patients pre-treated with ICIs for melanoma | Relatlimab plus nivolumab | ORR: 16%; DCR: 45% Any grade AEs rate: 46%; Grade 3–4 AEs rate: 9% |
| RELATIVITY-047 (placebo-controlled, randomized, phase II/III trial) [73] |
714 patients with previously untreated advanced melanoma | Relatlimab plus nivolumab vs. placebo plus nivolumab | Median PFS: 10.1 vs. 4.6 months; HR: 0.75 (95% CI: 0.62–0.92; p = 0.006) Grade 3–4 AEs rate: 18.9% vs. 9.7% |
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| TIM-3 | Sabatolimab | Curigliano et al. (phase I/II trial) [75] |
219 patients with solid tumors | Escalating doses of sabatolimab alone or sabatolimab plus spartalizumab | MTD not reached No response with sabatolimab alone ORR (sabatolimab plus spartalizumab): 6% |