Table 2.
Published clinical trials with therapeutics targeting the immune tumor microenvironment.
| Diagnosis | Therapeutics | Molecular Target | Target Cells | Trial Phase | Trial Name (Clinicaltrials.Gov Identifier) | Patients (N) | Clinical Setting | Clinical Response | Clinical Outcome | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| DLBCL | Ipilimumab | CTLA-1 | T cells | I | (NCT00089076) | 3 | R/R | ORR 33% (33% CR) | TTP 31+ mo | Ansell, Hurvitz et al. 2009 |
| Nivolumab | PD-1 | T cells | Ib | (NCT01592370) | 11 | R/R | ORR 36% (18% CR) | mPFS 7 wks | Lesokhin, Ansell et al. 2016 | |
| Nivolumab | PD-1 | T cells | II | (NCT02038933) | 121 | Ansell, Minnema et al. 2019 | ||||
| 87 | auto-HCT-failed | ORR 10% (3% CR) | mTTP 11 mo | |||||||
| 34 | auto-HCT-ineligible | ORR 3% (0% CR) | mTTP 8 mo | |||||||
| Nivolumab + ibrutinib | PD-1 + BTK | T cells + B cells | I–IIa | (NCT02329847) | 45 | R/R | ORR 36% (16% CR) | mPFS 2.1 mo | Younes, Brody et al. 2019 | |
| Pidilizumab | PD-1 | T cells | Ib | (NCT00532259) | 66 | post- auto-HCT | 16-mo PFS 0.72 | Armand, Nagler et al. 2013 | ||
| 35 | with measurable disease post-auto-HCT | ORR 51% (CR 34%) | ||||||||
| Hu5F9-G4 + rituximab | CD47 + CD20 | Tumor cells | Ib | (NCT02953509) | 15 | R/R | ORR 40% (33% CR) | mDOR n.r. at 6.2 mo | Advani, Flinn et al. 2018 | |
| PCNSL | Nivolumab | PD-1 | T cells | Ib | n/a | 5 (1 PTL with CNS engagement) | R/R | ORR 100% (80% CR) | PFS 13+ -17+ mo | Nayak, Iwamoto et al. 2017 |
| PMBCL | Pembrolizumab | PD-1 | T cells | Ib | KEYNOTE-013 (NCT01953692) | 17 | R/R | ORR 41% (12% CR) | DOR 2.3+ - 22.5+ mo | Zinzani, Ribrag et al. 2017 |
| FL | Ipilimumab | CTLA-1 | T cells | I | (NCT00089076) | 14 | R/R | ORR 7% (0% CR) |
TTP 19 mo | Ansell, Hurvitz et al. 2009 |
| Nivolumab | PD-1 | T cells | Ib | (NCT01592370) | 10 | R/R | ORR 40% (10% CR) | N/R | Lesokhin, Ansell et al. 2016 | |
| Nivolumab + ibrutinib | PD-1 + BTK | T cells + B cells | I–IIa | (NCT02329847) | 40 | R/R | ORR 33% (10% CR) | mPFS 9.1 mo | Younes, Brody et al. 2019 | |
| Pembrolizumab + rituximab | PD-1 + CD20 | T cells + B cells | II | n/a | 32 | R/R | ORR 67% (50% CR) | mPFS 11.4 mo | Nastoupil L, et al. 2017 | |
| Hu5F9-G4 + rituximab | CD47 + CD20 | Tumor cells | Ib | (NCT02953509) | 7 | R/R | ORR 71% (43% CR) | mDOR n.r. at 8.1 mo | Advani, Flinn et al. 2018 | |
| CLL | Nivolumab + ibrutinib | PD-1 + BTK | T cells + B cells | I–IIa | (NCT02329847) | 36 | R/R | ORR 61% (0% CR) | mPFS N/A | Younes, Brody et al. 2019 |
| Pembrolizumab | PD-1 | T cells | II | (NCT02332980) | 16 | R/R | ORR 0% | mPFS 2.4 mo | Ding, LaPlant et al. 2017 | |
| 9 | prior ibrutinib | ORR 0% | ||||||||
| RT | Nivolumab + ibrutinib | PD-1 + BTK | T cells + B cells | I–IIa | (NCT02329847) | 20 | R/R | ORR 65% (10% CR) | mPFS 5 mo | Younes, Brody et al. 2019 |
| Pembrolizumab | PD-1 | T cells | II | (NCT02332980) | 9 | R/R | ORR 44% (11% CR) | mPFS 5.4 mo | Ding, LaPlant et al. 2017 | |
| 6 | prior ibrutinib | ORR 100% | ||||||||
| cHL | Nivolumab | PD-1 | T cells | I | (NCT01592370) | 23 | R/R | ORR 87% (CR 17%) | 6mo PFS 86% | Ansell, Lesokhin et al. 2015 |
| Nivolumab | PD-1 | T cells | II | CheckMate 205 (NCT02181738) |
243 | R/R | Armand, Engert et al. 2018 | |||
| 63 (cohort A) | failed auto-HCT, BV-naïve | ORR 65% (29% CR) | mPFS 18.3 mo | |||||||
| 80 (cohort B) | failed auto-HCT and BV after | ORR 68% (13% CR) | mPFS 14.7 mo | |||||||
| 100 (cohort C) | failed auto-HCT, BV before and/or after auto-HCT | ORR 73% (12% CR) | mPFS 11.9 mo | |||||||
| Nivolumab + Brentuximab Vedotin | PD-1 + CD30 | T cells + HRS cells | I–II | (NCT02572167) | R/R | Herrera, Moskowitz et al. 2018 | ||||
| 60 (groups 1–2) | ORR 82% (61% CR) | 9-mo PFS* 86% 15-mo PFS* 82% |
||||||||
| 30 (group 3) | ORR 93% (80% CR) | 9-mo PFS* 88% | ||||||||
| Pembrolizumab | PD-1 | T cells | I | KEYNOTE-013 (NCT01953692) | 31 | R/R, prior BV 71% prior auto-HSC | ORR 65% (16% CR) | 6-mo PFS 69% 1-yr PFS 46% |
Armand, Shipp et al. 2016 | |
| Pembrolizumab | PD-1 | T cells | II | KEYNOTE-087 (NCT02453594) | R/R | Chen, Zinzani et al. 2017 | ||||
| 69 (cohort 1) | failed auto-HCT and BV | ORR 74% (22% CR) | ||||||||
| 81 (cohort 2) | failed salvage incl. BV | ORR 64% (25% CR) | ||||||||
| 60 (cohort 3) | failed auto-HCT, no BV | ORR 70% (20% CR) | ||||||||
| Pembrolizumab | PD-1 | T cells | II | (NCT02362997) | 30 | consolidation after auto-HCT | 18-mo PFS 82% 18-mo OS 100% |
Armand, Chen et al. 2019 |
DLBCL = diffuse large B cell lymphoma; PCNSL = primary central nervous system (CNS) lymphoma; PMBCL = primary mediastinal large B-cell lymphoma; FL = follicular lymphoma; cHL = classical Hodgkin lymphoma; PTL = primary testicular lymphoma; RT = Richter transformation; R/R = relapsed/refractory; ORR = overall response rate; CR = complete response; mTTP = median time to progression; mDOR = median duration of response; N/A = not assessable; N/R = not reported; n.r. = not reached; mPFS = median progression-free survival; mo = months; wks = weeks; auto-HCT = autologous stem cell transplantation; HRS = Hodgkin Reed-Sternberg; BTK = Bruton’s tyrosine kinase. * estimated.