From: Exploiting RIG-I-like receptor pathway for cancer immunotherapy
Category | Agent | Combination | Disease | Phase | Outcome | Identifier | References |
---|---|---|---|---|---|---|---|
5′-pppRNA | MK-4621 | Pembrolizumab | Solid tumors | I | OR with MK-4621 monotherapy, 0; SD, 4 (27%). PR with combination therapy, 3 (10%) | NCT03065023 NCT03739138 | [280] |
Synthetic dsRNA | BO-112 | Nivolumab or pembrolizumab | Tumors that had primary resistance to anti-PD-1 | I | PR and SD with combination therapy at 8–12 weeks, 3/28 (10.7%) and 10/28 (35.7%), respectively | NCT02828098 | [287] |
Peptide-complexed ssRNA with poly-U repeats | CV8102 | HepaVac-101 (therapeutic vaccine) | HCC | I/II | Immune responses against ≥ 1 vaccinated HLA class I and II TAA, 37% and 53%, respectively | NCT03203005 | [282] |
ssRNA | CV8102 | Anti-PD-1 therapy | Advanced melanoma; squamous cell carcinoma of the skin, head and neck; adenoid cystic cancer | I | Estimated study completion date, February 2023 | NCT03291002 | [281] |
Oncolytic virus | T-VEC | Pembrolizumab | Advanced/metastatic sarcoma | II | Best ORR at 6 mo: 30%. ORR overall, 35% | NCT03069378 | [291] |
Oncolytic virus | VSV | Ruxolitinib phosphate | Advanced treatment-refractory T cell lymphoma | I | 3/7 patients with T-cell lymphoma had responses: 2 PR at 3 mo and 6 mo, respectively; 1 CR ongoing at 20 mo | NCT03017820 | [292] |
Oncolytic virus | Pexa-Vec/ JX-594 | Metronomic cyclophosphamide | Advanced/metastatic soft tissue sarcoma | II | Combination therapy is not superior to metronomic cyclophosphamide alone (median PFS, 1.7 mo vs 7 mo; OS, 14.2 mo vs not reached | NCT02630368 | [297] |
Oncolytic virus | Pexa-Vec | Avelumab | Soft tissue sarcoma | I/II | Ongoing | NCT02630368 | / |
Oncolytic virus | Pexa-Vec | Surgical treatment | Colorectal cancer liver metastases or metastatic melanoma | II | Presurgical treatment with Pexa-Vec was associated with IFNα and chemokine induction, resulting in transient innate and long-lived adaptive anticancer immunity | EudraCT number 2012–000,704-15 | [298] |
Oncolytic virus | Pelareorep (reovirus) | Paclitaxel | Metastatic breast cancer | II | Median adjusted PFS (combination therapy vs paclitaxel alone), 3.78 mo vs 3.38 mo; Median OS (combination therapy vs paclitaxel alone), 17.4 mo vs 10.4 mo | NCT01656538 | [303] |
Oncolytic virus | Pelareorep | Pembrolizumab, and either 5-fluorouracil, gemcitabine, or irinotecan | Advanced pancreatic adenocarcinoma | Ib | Partial response for 17.4 mo, 1/10; SD, 2/10, lasting 9 and 4 mo, respectively | NCT02620423 | [305] |
Viral mimicry | Azacitidine | Nivolumab | Relapsed/refractory AML | Ib/II | ORR,33%; CR, 22%; 1 PR, 10% with hematologic improvement maintained > 6 mo. SD (> 6 mo), 10%; ORR was 58% and 22%, in hypomethylating agent-naïve and HMA-pretreated patients, respectively | NCT02397720 | [307] |
Viral mimicry | Azacitidine | Camrelizumab | Relapsed/refractory classical Hodgkin lymphoma | II | CR, 79% in the decitabine-plus-camrelizumab group vs 32% in camrelizumab group. Median PFS with decitabine-plus-camrelizumab therapy, 35.0 mo; 15.5 mo with camrelizumab monotherapy | NCT02961101 NCT03250962 | [311] |
Viral mimicry | Decitabine | Camrelizumab | Relapsed/refractory classical Hodgkin lymphoma after prior anti-PD-1 monotherapy | II | ORR, 52%; CR, 36% in the test cohort. ORR, 68%; CR, 24% in the expansion cohort. Median PFS in the test cohort and expansion cohort, 20 and 21.6 mo, respectively | NCT02961101 NCT03250962 | [312] |
Viral mimicry | Guadecitabine | Pembrolizumab | Advanced solid tumors | I | ORR, 7% with 37% achieving disease control (PFS) for ≥ 24 weeks. 5/12 (42%) NSCLC patients have disease control ≥ 24 weeks | NCT02998567 | [314] |
Viral mimicry | Entinostat | Pembrolizumab | Metastatic uveal melanoma | II | ORR,14%. CBR 18 weeks, 28%; median PFS2.1 months; median OS, 13.4 months. Toxicities were manageable, and there were no treatment-related deaths | NCT02697630 | [316] |
Chemotherapy | Capecitabine and oxaliplatin | Pembrolizumab | Advanced biliary tract carcinoma | II | PR, 27.3%; SD, 54%. Disease control rate, 81.8%. Median PFS, 4.1 mo with a 6 mo PFS rate of 45.5% | NCT03111732 | [319] |