Table 2 Current status of clinical trials testing combinations of HMA (epigenetic priming) with strategies targeting checkpoint receptors/ligands

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