Table 2.
Current status of clinical trials testing combinations of HMA (epigenetic priming) with strategies targeting checkpoint receptors/ligands
| HMA (Synonym) [Application Route] |
Checkpoint Target (Synonym) | Compound (Synonym) [Application Route] |
Status (design) | Indication | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|
| Azacitidine (CC-486) [p.o., 300 mg d1-15] |
CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [i.v., 200 mg Q3W] |
Phase II (non-randomized) | Metastatic melanoma, other skin neoplasms | NCT02816021 |
| Azacitidine (CC-486) [p.o., 300 mg d1-14, Q3W] |
CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [i.v., 200 mg Q3W, d1] |
Phase II (randomized) • MK-3475 + CC-486 • MK-3475 + placebo |
Previously treated locally advanced or metastatic NSCLC | NCT02546986 |
| Azacitidine [s.c., 100 mg d1-5, Q4W] | CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [i.v., 200 mg Q3W] |
Phase II (non-randomized) | Chemo-refractory metastatic CRC | NCT02260440 |
| Azacitidine [s.c./i.v., 75 mg/m2 d1-7 Q4W] | CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [200 mg i.v., Q3W, d8] |
Phase II (non-randomized) | Relapsed/refractory AML and newly diagnosed AML >65 years | NCT02845297 |
| Azacitidine (CC-486) [p.o., 300 mg d1-14 or d1-21, Q4W] |
CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [200 mg i.v., Q3W] |
Phase II (randomized) • CC-486 100 mg + MK-3475 • CC-486 100 mg BID + MK-3475 • CC-486 300 mg d1-14 + MK-3475 • CC-486 300 mg d1-21 + MK-3475 |
Platinum resistant ovarian, fallopian tube or primary peritoneal cancer | NCT02900560 |
| Azacitidine (CC-486) [p.o., 300 mg d1-14 or d1-21, Q4W] +/- Romidepsin (HDAC-I) [7 or 14 mg/m2, d1,8,15, Q4W] |
CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [200 mg i.v., Q4W, d1 + 15] |
Phase I (randomized) • CC-486 + MK-3475 • Romidepsin + MK-3475 • CC-486 + Romidepsin + MK-3475 |
Microsatellite stable advanced CRC | NCT02512172 |
| Guadecitabine (SGI-110) [s.c., d1-4, Q4W] |
CD279 (PD1) | Pembrolizumab (Lambrolizumab, MK-3475) [200 mg i.v., Q4W, d5] |
Phase II (non-randomized) | Platinum resistant ovarian, fallopian tube or primary peritoneal cancer | NCT02901899 |
| Azacitidine [s.c., 40 mg/m2, d1-6, d8-10, Q4W] +/- Entinostat (HDAC-I) [p.o., 8 mg, d3 + 10, Q4W] |
CD279 (PD1) | Nivolumab (BMS-936558, MDX-1106) [i.v., 3 mg/kg, Q2W] |
Phase II (randomized, sequential) • 2 cycles AZA + Romidepsin, followed by Nivolumab • Nivolumab |
Recurrent metastatic NSCLC | NCT01928576 |
| THU-decitabine [p.o., 10 mg/kg/0.2 mg/kg, d1-2, Q1W] |
CD279 (PD1) | Nivolumab (BMS-936558, MDX-1106) [i.v., 3 mg/kg, Q2W] |
Phase II (randomized) • 2 cycles AZA + Romidepsin, followed by Nivolumab • Nivolumab |
2nd line therapy for NSCLC | NCT02664181 |
| Azacitidine [s.c./i.v., 75 mg/m2 d1-7 Q4W] |
CD279 (PD1) | Nivolumab (BMS-936558, MDX-1106) [i.v., 3 mg/kg, Q4W, d1 + 14] |
Phase II (non-randomized) | Relapsed/refractory AML and newly diagnosed AML >65 years | NCT02397720 |
| Azacitidine [s.c./i.v., 75 mg/m2 d1-7, Q4W] Lirilimab (anti-KIR mAb) [d7, Q4W] |
CD279 (PD1) | Nivolumab (BMS-936558, MDX-1106) [i.v., 3 mg/kg, Q4W, d7 + 21] |
Phase II (non-randomized) | High-risk MDS | NCT02599649 |
| Azacitidine [s.c., 75 mg/m2 d1-5, Q4W] |
CD279 (PD1) CD152 (CTLA-4) |
Nivolumab (BMS-936558, MDX-1106) [i.v., 3 mg/kg, Q3W, d6] Ipilimumab (BMS-73406, MDX-010) [i.v., 3 mg/kg, Q3W, d6] |
Phase II (non-randomized, parallel assignment) • AZA + Nivolumab • AZA + Ipilimumab • AZA + Nivolumab + Ipilimumab |
Previously untreated MDS | NCT02530463 |
| Decitabine [d1-5, Q4W] |
CD152 (CTLA-4) | Ipilimumab (BMS-73406, MDX-010) [i.v., 3 mg/kg, Q8W, d1] |
Phase I (non-randomized) | Relapsed/refractory post allo-HSCT MDS RAEB I/II or AML | NCT02890329 |
| SGI-110 [30 mg/m2, d1-5, Q3W] |
CD152 (CTLA-4) | Ipilimumab (BMS-73406, MDX-010) [i.v., 3 mg/kg, Q3W] |
Phase I (non-randomized) | Unresectable or metastatic melanoma | NCT02608437 |
| Azacitidine [s.c., 75 mg/m2, d1-7, Q4W] |
CD152 (CTLA-4) CD274 (PD-L1) |
Tremelimumab (CP-675,206) Durvalumab (MEDI-4736) |
Phase I (non-randomized) • Tremelimumab + Ipilimumab • AZA + Tremelimumab + Ipilimumab |
MDS relapsed/refractory to HMA | NCT02117219 |
| Azacitidine (CC-486) [p.o., 300 mg d1-14, Q4W] |
CD274 (PD-L1) | Durvalumab (MEDI-4736) [i.v., 1500 mg, Q4W, d1] |
Phase II (non-randomized) | Microsatellite stable CRC, platinum-resistant ovarian cancer, ER+ and HER2- breast cancer | NCT02811497 |
| Azacitidine [s.c., 75 mg/m2, d1-7, Q4W] |
CD274 (PD-L1) | Durvalumab (MEDI-4736) [i.v., 1500 mg, Q4W, d1] |
Phase II (randomized) • AZA + Durvalumab • AZA |
Previously untreated high-risk MDS or AML >65 years ineligible for allo-SCT | NCT02775903 |
| Azacitidine (CC-486) [p.o., 200 mg d1-21, Q4W] |
CD274 (PD-L1) | Durvalumab (MEDI-4736) [i.v.] |
Phase II (randomized) • CC-486 + Durvalumab • CC-486 |
MDS refractory to Azacitidine or Decitabine | NCT02281084 |
| Azacitidine [s.c., 75 mg/m2, d1-7 or d1-5 + 8-9, Q4W] |
CD274 (PD-L1) | Azetolizumab (MPDL-3280A) (RG7446) [i.v., 840 mg, d1 + 22, Q4W] |
Phase II (non-randomized) | HMA naive or relapsed/refractory MDS | NCT02508870 |
| Azacitidine [s.c. or i.v., 75 mg/m2, d1-7, Q4W] |
CD274 (PD-L1) | Avelumab (MSB-0010718C) [i.v., 3 mg/kg, d1 = +14, Q4W] |
Phase I/II (non-randomized) | Relapsed/refractory AML | NCT02953561 |