Table 1.
Efficacy in select phases 2 and 3 clinical trials of idelalisib and duvelisib in CLL/SLL
| Trial | Phase 3, idelalisib + rituximab vs rituximab in R/R CLL8,9 | Phase 3, idelalisib vs placebo + BR in R/R CLL14 | Phase 3, idelalisib + ofatumumab vs ofatumumab in previously treated CLL13 | Phase 3, acalabrutinib vs investigator’s choice (BR or idelalisib + rituximab) in R/R CLL10 | Phase 2, treatment-naïve older patients with CLL, idelalisib + rituximab11 | Phase 2, treatment-naïve CLL with idelalisib + ofatumumab12 | Phase 2, DYNAMO trial, double-refractory FL, SLL, MZL22 | Phase 3, DUO trial, duvelisib vs ofatumumab in R/R CLL/SLL21 |
|---|---|---|---|---|---|---|---|---|
| Population | R/R CLL | R/R CLL | R/R CLL | R/R CLL | Treatment-naïve older patients with CLL/SLL | Treatment-naïve patients with CLL | iNHL (FL, SLL, or MZL) double-refractory to rituximab + chemoimmunotherapy or radioimmunotherapy | R/R CLL/SLL |
| Treatment | Idelalisib 150 mg by mouth twice daily plus rituximab IV 375 mg/m2 in week 0, day 1, and 500 mg/m2 day 1 of weeks 2, 4, 6, 8, 12, 16, and 20 vs rituximab + placebo | Bendamustine 70 mg/m2 IV on days 1 and 2 C1-6 plus rituximab: 375 mg/m2 on C1D1, and 500 mg/m2 D1C2–6 plus idelalisib 150 mg twice daily vs BR plus placebo | Ofatumumab 300 mg in week 1, day 1 followed by 2000 mg weekly for 7 wk, then every 4 wk for 16 wk vs idelalisib 150 mg by mouth twice daily plus ofatumumab on same week schedule as control group but at 1000 mg from week 2 | Acalabrutinib 100 mg by mouth twice daily vs investigator’s choice of idelalisib 150 mg by mouth twice daily plus rituximab 375 mg/m2 on C1D1 and 500 mg/m2 D1C2–6 or bendamustine 70 mg/m2 IV on days 1 and 2 C1-6 plus rituximab | Idelalisib 150 mg by mouth twice daily plus rituximab 375 mg/m2 IV weekly for 8 wk | Idelalisib 150 mg by mouth twice daily plus ofatumumab 300 mg C3D1 followed by 1000 mg weekly for 7 wk, then 100 mg every 4 wk for 16 wk (6 mo total) | Duvelisib 25 mg by mouth twice daily | Duvelisib 25 mg twice daily or ofatumumab IV for up to 12 doses |
| Number of patients | 220 | 416 | 261 | 398 | 64 | 27 | 129 | 159 |
| Primary endpoint | PFS | PFS | PFS | PFS | ORR | ORR | ORR | PFS |
| mPFS | Not reached at 12 mo for idelalisib + R vs 5.5 mo in placebo arm; P < .001; 20.3 mo (17.3−26.3 mo) at 18-mo follow-up | 20.8 mo (16.6-26.4) for idelalisib arm vs 11.1 mo (8.9-11.1) in placebo arm (P < .0001) at 14-mo follow-up | 16.3 mo (13.6-17.8) in idelalisib plus ofatumumab arm vs 8.0 mo (5.7-8.2) with ofatumumab (P < .0001) | Acalabrutinib monotherapy (PFS NR) vs investigator’s choice (16.5 mo; hazard ratio, 0.31; P < .0001) at 16.1-mo follow-up | mPFS was not reached; PFS at 12, 18, and 24 mo was 92.9%, at 36 mo was 82% (64%-92%) | 23 mo (18-36) | 9.5 mo (8.1-11.8) | 13.3 mo in duvelisib arm vs 9.9 mo in ofatumumab arm (P < .0001) |
| ORR (CRs) in PI3Ki arm | 85.5% (1 patient with CR) | 70% (1%) | 75.3% (1 patient; <1%) | NR separately for idela + R vs BR in investigator’s choice arm | 96.9% (14.1%) | 88.9% (1 patient with CR) | 47.3% (1.6%) entire population SLL, 67.9% FL, 42.2%; MZL: 38.9% |
73.8% (1 patient with CR) |
| OS | mOS was 40.6 mo (28.5-57.3) vs 34.6 mo (16.0-NR) | Not adequately powered to show OS benefit | mOS not reached and not different from control | mOS not reached | mOS not reached; at 36 mo, was 90% (82%-99%) | mOS not reached; at 36 mo, was 88% (68%-96%) | mOS was 28.9 mo (21.4-NE); 1-y OS estimate of 77% | mOS not reached in either arm, with 12-mo OS of 86% (0.65-1.50) for both treatment arms |
C3D1, cycle 3, day 1; C1-6, cycles 1-6; C1D1, cycle 1, day 1; CR, complete response; D1C2-6, day 1 cycles 2-6; FL, follicular lymphoma; iNHL, indolent non-hodgkin lymphoma; mPFS, median progression free survival; mOS, median overall survival; MZL, marginal zone lymphoma; NR, not reached.