Table 2.
Clinical trials combining immune checkpoint blockade with targeting of immunosuppressive molecules.
| Trial identifier/study phase/status | Combination therapy | Patient condition | Sponsor | Official study title | Study design |
|---|---|---|---|---|---|
| NCT02743819 Phase II (recruiting, 2016) | • Pembrolizumab (antagonist PD-1 mAb) • ipilimumab [antagonist (CTLA-4) mAb] | Metastatic melanoma (MM) | University of Chicago | Phase II study of pembrolizumab and ipilimumab following initial anti-PD1/L1 antibody | Pembrolizumab plus ipilimumab. • Arm A: progression on anti-PD1/L1 antibody • Arm B: stable disease more than 24 weeks or initial response on anti-PD1/L1 antibody |
| NCT02381314 Phase I (recruiting, 2015) | • Ipilimumab (antagonist CTLA-4 mab) • enoblituzumab (B7-H3 mAb) | Metastatic tumors including MM | MacroGenics | A Phase 1, open-label, dose escalation study of MGA271 in combination with ipilimumab in patients with melanoma, non-small-cell lung cancer, and other cancers | Enoblituzumab will be administered IV once/week (51 doses) to determine maximum tolerated dose (MTD) in combination with ipilimumab, which is administered IV/3 weeks/four doses |
| NCT02460224 Phase I/II (recruiting, 2015) | • PDR001 (antagonist PD-1 mAb) • LAG525 (antagonist LAG-3 mAb) | Metastatic tumors including MM | Novartis Pharmaceuticals | A Phase I/II, open label, multicenter study of the safety and efficacy of LAG525 single agent and in combination with PDR001 administered to patients with advanced malignancies | • Arm A: LAG525 single treatment arm. • Arm B: LAG525 plus PDR001 combination arm. • Arm C: LAG525 single treatment arm in Japanese patients |
| NCT02655822 Phase I (recruiting, 2016) | • CPI-444 (blocking adenosine-A2A receptor inhibitor) • atezolumab (antagonist PD-L1 mAb) | Metastatic tumors including MM | Corvus Pharmaceuticals, Inc. | A Phase 1/1b, open-label, multicenter, repeat-dose, dose-selection study of CPI-444 as single agent and in combination with atezolizumab in patients with selected incurable cancers | • Cohort I: CPI-444 100 mg orally twice daily for the first 14 days/each 28-day cycle. • Cohort II: CPI-444 100 mg orally twice daily for 28 days/each 28-day cycle. • Cohort III: CPI-444200 mg orally once daily for the first 14 days/each 28-day cycle. • Cohort IV: CPI-444 MTD + atezolizumab IV |
| NCT02817633 Phase I (recruiting, 2016) | • Antagonist PD-L1 mAb • TSR-022 (antagonist Tim-3 mAb) | Metastatic tumors including MM | Tesaro, Inc. | A Phase 1 dose escalation and cohort expansion study of TSR-022, an Anti-TIM-3 monoclonal antibody, in patients with advanced solid tumors | • Part 1: Dose Escalation. 1a: dose escalation TSR-022 alone. 1b: dose escalation TSR-022 plus anti-PD-1 antibody. 1c: Phase 2 TSR-022 MTD plus anti-PD-1 antibody. • Part 2: expansion cohorts of Part 1 |
| NCT02608268 Phase I/II (recruiting, 2015) | • PDR001 (antagonist PD-1 mAb) • MBG453 (antagonist Tim-3 mAb) | Metastatic tumors including MM | Novartis Pharmaceuticals | Phase I–Ib/II open-label multi-center study of the safety and efficacy of MBG453 as single agent and in combination with PDR001 in adult patients with advanced malignancies | • Cohort 1: MBG453 dose escalation. • Cohort 2: MBG453 dose escalation in combination with PDR001 |
| NCT02983006 Phase I (recruiting, 2016) | • Nivolumab (antagonist PD-L1 mAb) • DS-8273a (TRAIL-DR5 mAb) | MM | New York University School of Medicine | A Phase 1 study of TRAIL-DR5 antibody DS-8273a administered in combination with nivolumab in subjects with unresectable Stage III or Stage IV melanoma | DS-8273a: starting dose 4 mg/kg IVQ 3 weeks. Dose Escalation: 8 mg/kg IV Q 3 weeks, 16 mg/kg IV Q 3 weeks, 24 mg/kg IV Q 3 weeks, 2 mg/kg IV Q 3 weeks, 4 mg/kg IV Q 3 weeks. • nivolumab: 5 mg/kg IV Q 3 weeks |
| NCT02471846 Phase I (recruiting, 2015) | • Atezolizumab (antagonist PD-1 mAb) • GDC-0919 (IDO inhibitor) | Metastatic tumors including MM | Genentech, Inc. | A Phase Ib, open-label, dose-escalation study of the safety and pharmacology of GDC-0919 administered with atezolizumab in patients with locally advanced or metastatic solid tumors | • Relapsed cohorts to PD1/PD-L1 blockade will receive GDC-0919 at MTD. • Untreated advanced patients will receive escalation doses of atezolizumab and GDC-0919 combinations. • An expansion cohort of atezolizumab and GDC-0919 combination at MTD |
| NCT02318277 Phase I/II (recruiting, 2014) | • Durvalumab (blocking PD-L1 mAb) • epacadostat (IDO-1 inhibitor molecule) | Metastatic tumors including MM (B7H3+) | Incyte Corporation | A Phase 1/2 study exploring the safety, tolerability, and efficacy of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) | Durvalumab IV at selected dose levels every 2 weeks plus epacadostat 25 mg BID as starting dose, followed by dose escalations until MTD |
| NCT02327078 Phase I/II (recruiting, 2014) | • Nivolumab (PD-1 antagonist mab) • epacadostat (IDO-1 inhibitor) | Metastatic tumors including MM | Incyte Corporation | A Phase 1/2 study of the safety, tolerability, and efficacy of epacadostat administered in combination with nivolumab in select advanced cancers (ECHO-204) | • Phase 1: nivolumab IV 3 mg/kg/2 weeks plus epacadostat 25 mg BID as starting dose, followed by dose escalations. • Phase 2: nivolumab 240 mg 2 weeks plus epacadostat MTD |
| NCT02073123 Phase I/II (recruiting, 2014) | • Ipilimumab (antagonist CTLA-4 mAb) • pembrolizumab (antagonist PD-1 mAb) • nivolumab (antagonist PD-1 mAb) • indoximod (IDO inhibitor) | MM | NewLink Genetics Corporation | A Phase 1/2 study of the concomitant administration of indoximod plus immune checkpoint inhibitors (CPIs) for adult patients with advanced or MM | • Indoximod 1,200 mg BID concurrently with ipilimumab IV 3 mg/kg/3 weeks/four doses. • Indoximod 1,200 mg BID and pembrolizumab IV at 2 mg/kg/3 weeks. • Indoximod 1,200 mg BID and nivolumab IV at 3 mg/kg/4 weeks |
| NCT02117362 Phase I (recruiting, 2014) | • Ipilimumab (antagonist CTLA-4 mAb) • GR-MD-02 (Galectin-3 Inhibitor) | MM | Providence Health & Services | Phase IB study of a galectin inhibitor (GR-MD-02) and ipilimumab in patients with MM | Cohorts with escalating doses of GR-MD-02 (1, 2, 4, 8 mg/kg) 1 hour before 3 mg/kg of ipilimumab on days 1, 22, 43, and 65 |
| NCT02403778 Phase II (ongoing, not-recruiting, 2015) | • Ipilimumab (CTLA-4 antagonist mab) • All-trans retinoic acid (ATRA) | MM | University of Colorado, Denver | Ipilimumab and ATRA combination treatment of Stage IV melanoma | • Arm A: ipilimumab 10 mg/kg/3 weeks/four doses. • Arm B: ipilimumab 10 mg/kg/3 weeks/four doses plus 150 mg/m2 ATRA orally for 3 days surrounding ipilimumab dosage |
| NCT02807844 Phase I/II (recruiting, 2016) | • PDR001 (antagonist PD-1 mAb) • MCS110 (blocking MCSF mAb) | Metastatic tumors including MM | Novartis Pharmaceuticals | A Phase Ib/II, open label, multicenter study of MCS110 in combination with PDR001 in patients with advanced malignancies | MCS110 combined with PDR001 |
| NCT02452424 Phase I/II (recruiting, 2015) | • Pembrolizumab (PD-1 mAb) • PLX3397 (CSF1R inhibitor) | Metastatic tumors including MM | Plexxikon | Phase 1/2a study of double-immune suppression blockade by combining a CSF1R inhibitor (PLX3397) with an Anti-PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors | • Part 1: open-label, sequential PLX3397 dose escalation with a fixed dose of pembrolizumab (200 mg, IV) in approximately 24 patients with advanced solid tumors. • Part 2: extension cohort |
| NCT02880371 Phase I/II (recruiting, 2016) | • Pembrolizumab (antagonist PD-1 mAb) • ARRY-382 (CSF1R) | Metastatic tumors including MM | Array BioPharma | A Study of ARRY-382 in combination with pembrolizumab, a programmed cell death receptor 1 (PD-1) antibody, for the treatment of patients with advanced solid tumors | • Part A: escalating doses of ARRY-382 with pembrolizumab 2 mg/kg. • Part B: ARRY-382 at MTD with pembrolizumab 2 mg/kg. • Part C: ARRY-382 at MTD with 200 mg pembrolizumab |