Table 1 Clinical trials of TIME and ICP co-targeted combination therapies in multiple cancers
TIME-targeting therapy | Effect | Combined ICP inhibitor | Indication | N | Response | Clinical trial | Status |
|---|---|---|---|---|---|---|---|
T-VEC | OV | Ipilimumab | Melanoma | 198 | ORR 39% (T-VEC + Ipi) vs. 18% (Ipi), P = 0.002 | NCT01740297 | Active, not recruiting |
T-VEC | OV | Pembrolizumab | Melanoma | 21 | ORR 48% | NCT02263508 | Active, not recruiting |
T-VEC | OV | Pembrolizumab | HNSCC | 36 | ORR 15.6%; disease control rate 40.6% | NCT02626000 | Active, not recruiting |
HF10 | OV | Ipilimumab | Melanoma | 46 | BORR at 24 weeks 41%; median PFS 19 m; median OS 21.8 m | NCT02272855 | Completed |
HF10 | OV | Nivolumab | Melanoma | 7 | Major pathological response 0% | NCT03259425 | Active, not recruiting |
Epacadostat | IDO1 inhibitor | Pembrolizumab | Gastric cancer and esophageal cancer | 3 | 6-month survival rate 33.3% | NCT03196232 | Completed |
Epacadostat | IDO1 inhibitor | Pembrolizumab | Head and Neck cancer | 54 | ORR 31.4% (Epa + Pem) vs. 21.1% (Pem) | NCT03358472 | Active, not recruiting |
Epacadostat | IDO1 inhibitor | Pembrolizumab | Lung cancer | 154 | ORR 32.5% (Epa + Pem) vs. 39% (Pem) | NCT03322540 | Active, not recruiting |
Epacadostat | IDO1 inhibitor | Pembrolizumab | RCC | 129 | ORR 31.3% (Epa + Pem) vs. 29.2% (SoC) | NCT03260894 | Active, not recruiting |
Epacadostat/platinum-based chemotherapy | IDO1 inhibitor/chemotherapy | Pembrolizumab | Lung cancer | 223 | ORR 26.4% (Epa + Pem+Chemo) vs. 44.8% (Pem + Chemo) | NCT03322566 | Active, not recruiting |
Azacitidine/epacadostat | DNA methyltransferase inhibitor/IDO1 inhibitor | Pembrolizumab | Advanced malignancies | 70 | 5.7% ORR | NCT02959437 | Completed |
Axitinib | VEGFR inhibitor | Pembrolizumab | RCC | 861 | median PFS 15.1 m (Axi + Pem) vs. 11.0 m (Suntinib), P = 0.00012; ORR 59.3% (Axi + Pem) vs. 35.7% (Suntinib), P < 0.0001 | NCT02853331 | Active, not recruiting |
Bevacizumab | VEGFR inhibitor | Atezolizumab | RCC | 915 | median PFS 11.2 m (Bev + Ate) vs. 7.5 m (Sunitinib), P = 0.0205 | NCT02420821 | Active, not recruiting |
Bevacizumab/capecitabine | VEGFR inhibitor | Atezolizumab | CRC | 133 | median PFS 4.37 m (Bev + Ate+Cap) vs. 3.32 m (Bev + Cap), P = 0.051; median OS 10.55 m (Bev + Ate+Cap) vs. 10.61 m (Bev + Cap), P = 0.40 | NCT02873195 | Active, not recruiting |
Bevacizumab | VEGF inhibitor | Atezolizumab | HCC | 356 | median PFS 6.8 m (Bev + Ate) and 4.3 m (Sunitinib), P < 0.001; 1-year survival rate 67.2% (Bev + Ate) vs. 54.6% (Sunitinib) | NCT03434379 | Active, not recruiting |
Bevacizumab/carboplatin+ paclitaxel | VEGF inhibitor/chemotherapy | Atezolizumab | NSCLC | 692 | median PFS 8.3 m (Bev + Chemo+Ate) vs. 6.8 m (Chemo + Bve), P < 0.001; median OS 19.2 m (Bev + Chemo+Ate) vs. 14.7 m (Chemo + Bve), P = 0.02 | NCT02366143 | Active, not recruiting |
Carboplatin/nab-paclitaxel/pemetrexed | Chemotherapy | Atezolizumab | NSCLC | 723 | median PFS 7.0 m (Ate + Nab+Pab+Car) vs. 5.5 m (Nab + Pab+Car), P < 0.001; median OS 18.6 m (Ate + Nab+Pab+Car) vs. 13.9 m (Nab + Pab+Car), P < 0.001 | NCT02367781 | Active, not recruiting |
Nab-paclitaxel | Chemotherapy | Atezolizumab | Triple-negative breast cancer | 900 | ITT median OS 21.0 m (Ate + Chemo) vs. 18.7 m (Chemo), P = 0.078 | NCT02425891 | Active, not recruiting |
Cisplatin/carboplatin/pemetrexed | Chemotherapy | Pembrolizumab | NSCLC | 616 | median PFS 8.8 m (Pem + Chemo) vs. 4.9 m (Chemo), P < 0.00001; ORR 47.6% vs. 18.9%, P < 0.0001 | NCT02578680 | Active, not recruiting |
Carboplatin/etoposide | Chemotherapy | Atezolizumab | NSCLC | 403 | median PFS 5.2 m (Ate + Chemo) vs. 4.3 m (Chemo), P = 0.0170; 12.3 m (Ate + Chemo) vs. 10.3 m (Chemo), P = 0.0069 | NCT02763579 | Active, not recruiting |
Carboplatin/nab-paclitaxel/pemetrexed | Chemotherapy | Pembrolizumab | NSCLC | 559 | median PFS 6.4 m (Pem + Chemo) vs. 4.8 m (Chemo), P < 0.0001; OS 15.9 m (Pem + Chemo) vs. 11.3 m (Chemo), P = 0.0008; ORR 57.9% (Pem + Chemo) vs. 38.4% (Chemo) | NCT02775435 | Active, not recruiting |
NKTR-214 | IL-2 therapy | Nivolumab/Ipilimumab | Melanoma, NSCLC | 38 | ORR 59.5%; DCR 83.8% | NCT02983045 | Active, not recruiting |
M7824 | Bifunctional fusion protein composed of a mAb against PD-L1 fused to a TGFβ | / | Solid Tumors | 19 | ORR 15.7% | NCT02517398 | Active, not recruiting |
