Table 2.
Selected Trials of PI3K Inhibitors
| Drug | Additional Agents |
Disease | Phase | Patient no. |
Median age (range) |
Mean time on therapy (mos)1 |
Median Follow-up (mos) |
ORR (CR) | Median PFS (mos) |
Neutropenia (All / Grade 3) |
Diarrhea (All / Grade 3) |
Transaminitis (All / Grade 3) |
NCT | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Idelalisib | ||||||||||||||
| - | R/R iNHL | 1 | 64 | 64 (32–91) | 9.3 | NR | 47% (1.6%) | 7.6 | 44 / 23 | 36/9 | 48/25 | NCT00710528 | [50] | |
| - | R/R CLL | 1 | 54 | 63 (37–82) | 15 | NR | 72% (0%) | 15.8 | 57/43 | 30/6 | 28/2 | NCT01090414 | [39] | |
| - | R/R MCL | 1 | 40 | 69 (52–83) | 6.3 | NR | 40% (5%) | 3.7 | 30/10 | 40/18 | 60/20 | NCT00710528 | [52] | |
| 101-08, 2 | - | 1L CLL | 2 | 37 | 70 | 4.8 | NR | 81% (0%) | NR | NR/20 | 8/3 | NR/8 | NCT01203930 | [102] |
| 101-08, 1 | rituximab | 1L CLL | 2 | 64 | 71 (65–90) | 22.41 | NR | 97% (19%) | Not reached | 53/28 | 64/42 | 67/23 | [103] | |
| ofatumumab | 1L CLL | 2 | 24 | 67 (58–85) | 7.71 | 14.7 | NR | NR | 46/29 | 46/17 | 79/54 | NCT02135133 | [60] | |
| 101-09 (DELTA) | - | R/R iNHL | 2 | 125 | 64 (33–87) | 6.61 | 9.7 | 57% (6%) | 11.0 | 56/27 | 43/13 | 47/13 | NCT01282424 | [51] |
| Gilead 116 | rituximab | R/R CLL | 3 | 110 | 71 | 5 | 13 | 77 | Not reached | 60/37 | 21/5 | 40/8 | NCT01539512 | [54] |
| Gilead 115 | BR | R/R CLL | 3 | 207 | 62 (656-69) | 14.8 | 14 | 70% (1%) | 20.8 | 64/60 | 38/9 | 61/21 | NCT01569295 | [55] |
| Gilead 119 | ofatumumab | R/R CLL | 3 | 174 | 68 (61–74) | 13.91 | 16.1 | 75% (<1%) | 16.3 | 71/47 | 54/23 | 53/11 | NCT01659021 | [56] |
| Duvelisib | ||||||||||||||
| - | R/R iNHL | 1 | 36 | 64 (37–78) | 11.81 | NR | 62% (21%) | Not reached | 22/22 | 32/16 | 47/37 | NCT01476657 | [68] | |
| - | R/R CLL | 1 | 54 | 66 (42–82) | NR | NR | 58% (2%) | 15.7 | 53/42 | 44/9 | 29/9 | [71] | ||
| - | 1L CLL | 1 | 18 | NR | 13.2 | NR | 82% (0%) | Not reached | NR/39 | NR/22 | NR/17 | [73] | ||
| DYNAMO | - | R/R iNHL | 2 | 129 | 65 (30–90) | 61 | 12 | 46% (0%) | 8.4 | 32/23 | 44/15 | 14/6 | NCT01882803 | [69] |
| CONTEMPO | rituximab | 1L FL | 1/2 | 28 | 58 | 3.9 | NR | 87% (22%) | NR | 14/11 | 46/14 | 32/25 | NCT02391545 | [75] |
| obinutuzumab | 1L FL | 1/2 | 27 | 58 | 4.5 | NR | 91% (18%) | NR | 22/22 | 26/11 | 44/26 | |||
| FCR | 1L CLL | 1/2 | 12 | 57 (46–65) | NR | NR | 100% (33%) | NR | 67/50 | 42/8 | 25/17 | NCT02158091 | [77] | |
| Umbralisib | ||||||||||||||
| - / ublituximab2 | R/R CLL | 1 | 43 | 65 (22–86) | NR | NR | 88%3 | 24,4 Not Reached5 | 21/18 | 47/3 | 8/3 | NCT01767766 | [80] | |
| - / ublituximab2 | R/R NHL | 1 | 122 | 53% | 274 | |||||||||
| ibrutinib | R/R MCL | 1 | 14 | 67 (50–83) | NR | 14 | 79% (9%) | 8.4 | 36/7 | 36/0 | 22/0 | NCT02268851 | [84] | |
| R/R CLL | 1 | 18 | 67 (48–86) | NR | 94% (6%) | Not reached | 38/17 | 28/0 | ||||||
| ublituximab, ibrutinib | CLL6 | 1 | 20 | 65 (32–85) | 11.1 | NR | 100% (32%) | NR | 32/18 | 47/3 | None reported | NCT02006485 | [85] | |
| ublituximab, ibrutinib | NHL | 1 | 18 | 91% (36%) | ||||||||||
| ublituximab and bendamustine | R/R DLBCL and FL | 1 | 68 (31–81) | NR | DLBCL: 63% (44%) FL: 88% (50%) | NR | 24/24 | 36/9 | None reported | NCT02006485 | [82] | |||
| Copanlisib | ||||||||||||||
| -7 | R/R NHL | 1 | 9 | 65 (33–86) | 101 | NR | 78% (11%) | NR | NR | 16/2 | NR | NCT00962611 | [87] | |
| CHRONOS-1 Part A | - | R/R iNHL | 2 | 33 | 68 (46–89) | 5.61 | NR | 44% (9%) | 9.8 | 39/33 | 39/3 | 34/6 | NCT01660451 | [89] |
| R/R aNHL8 | 2 | 34 | 63 (22–90) | 2.01 | NR | 27% (8%) | 2.3 | 31/28 | 41/6 | 24/2 | ||||
| CHRONOS-1 Part B | - | R/R iNHL | 2 | 142 | NR | NR | NR | 59% (12%) | 11.3 | 25/19 | 18/4 | 28/NR | [90] | |
| - | R/R DLBCL | 2 | 67 | 69 (25–93) | NR | NR | 25% (12.5%)9 | NR | NR | 36/2 | NR | NCT02391116 | [90,91] | |
| RP-6530 | ||||||||||||||
| - | R/R NHL10 | 1 | 26 | 59 (20–83) | 2.5 | NR | 20% (10%) | NR | None reported | None reported | None reported | NCT02017613 | [92] | |
| INCB050465 | ||||||||||||||
| - | R/R NHL | 1 | 52 | 65 (30–88) | 3.31 | NR | 61% (32%) | NR | NR/21 | 31/6 | NR/0 | NCT02018861 | [94] | |
| ACP-319 | ||||||||||||||
| - | R/R NHL | 1 | 28 | 68 | NR | NR | NR | NR | NR | NR/10% | NR/4% | NCT01300026 | [97] | |
1L = first line, BO = bendamustine plus obinutuzumab, BR = bendamustine plus rituximab, FL = follicular lymphoma, FCR = fludarabine, cyclophosphamide, and rituximab, iNHL = indolent non-Hodgkin lymphoma, MCL = mantle cell lymphoma, MZL = marginal zone lymphoma, NR = not reported, Ofa = ofatumumab, R/R = relapsed/refractory, R-CHOP = rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone
In certain trials, only median time on therapy was provided. Time on therapy refers to time on PI3K inhibitor if multiple agents were involved.
Results of monotherapy and combination therapy with ublituximab were reported together.
Response rate restricted to 16 patients who received the phase 3 dose.
ORR in patients treated with umbralisib monotherapy.
ORR in patients treated with umbralisib plus ublituximab.
Three CLL patients were treatment naïve.
This trial enrolled both patients with solid and liquid malignancies. Median time on therapy and response rates are for NHL only. Age and toxicities are for all enrolled subjects.
The aggressive non Hodgkin lymphoma cohort included patients with DLBCL, FL grade 3b, MCL, mediastinal large B-cell lymphoma, peripheral T cell lymphoma, and transformed FL.
ORR and CR rate are for the 40 patients included in the per-protocol analysis (i.e. those who received at least three doses of drug and had pre- and post-treatment CT scans for comparison)
Diseases included Hodgkin lymphoma (9), T-cell lymphoma (4), DLBCL (4), MCL (3), CLL/SLL (2), FL (1), MZL (1), lymphoplasmacytic lymphoma (1), and multiple myeloma (1).