Table 2.
Ongoing clinical trials combining ICI blockades and agents related to neutrophil biology.
| Ongoing Trials | Neutrophil Biology Targets | Agents | ICI Targets | ICIs | Cancer | First Posted | Phase | Status | Results |
|---|---|---|---|---|---|---|---|---|---|
| NCT02851004 | STAT3 | BBI-608 | PD-1 | Pembrolizumab | Metastatic CRC | 2016 | Phase Ib/II | Terminated | / |
| NCT03647839 | PD-1 | Nivolumab | MSS Metastatic CRC | 2018 | Phase II | Completed | Not available | ||
| NCT02983578 | Danvatirsen/AZD9150 | PD-L1 | Durvalumab | dMMR CRC | 2016 | Phase II | Active, not recruiting | / | |
| NCT03168139 | CXCL12/CXCR4/CXCR7 | NOX-A12/Olaptesed | PD-1 | Pembrolizumab | Metastatic CRC | 2017 | Phase I/II | Completed | A total of 70% were still alive at 24 weeks, and 50% at 36 weeks. A total of 27% CRC patients achieved SD based on data from the 2018 ESMO Immuno-Oncology Congress. |
| NCT03473925 | CXCR1/2 | Navarixin | PD-1 | Pembrolizumab | Advanced/Metastatic Solid Tumors (MSS CRC) | 2018 | Phase II | Completed | A total of 19 participants with MSS CRC were enrolled in a low-dose group (30 mg navarixin plus 200 mg pembrolizumab), and 21 participants in a high-dose group (100 mg navarixin plus 200 mg pembrolizumab). The median PFS was 1.8 months (95% CI, from 1.0 to 2.0) in the low-dose group, and 1.9 months (95% CI, from 1.6 to 2.0) in the high-dose group. The median OS was 6.5 months (95% CI, from 3.0 to 9.7) in the low-dose group, and 8.0 months (95% CI, from 5.7 to 14.4) in the high-dose group. |
| NCT04599140 | SX-682 | PD-1 | Nivolumab | RAS-Mutated, MSS Metastatic CRC | 2020 | Phase Ib/II | Recruiting | / | |
| NCT03184870 | CCR2/5 | BMS-813160 | PD-1 | Nivolumab | Advanced Solid Tumors (CRC) | 2017 | Phase Ib/II | Active, not recruiting | / |
| NCT03631407 | CCR5 | Vicriviroc | PD-1 | Pembrolizumab | MSS Metastatic CRC | 2018 | Phase II | Completed | A total of 41 participants with MSS CRC were randomized to receive vicriviroc (low-dose: 150 mg; high-dose: 250 mg) in combination with pembrolizumab (200 mg). The ORRs of the two groups were both 5.0% (95% CI, from 0.1 to 24.9%). The median PFS was 2.1 months (95% CI, from 1.8 to 3.0) in the low-dose group, and 2.1 months (95% CI, from 1.6 to 3.9) in the high-dose group. The median OS was 4.6 months (95% CI, from 2.7 to 12.6) in the low-dose group, and 5.3 months (95% CI, from 3.2 to 8.0) in the high-dose group. |
| NCT04721301 | Maraviroc | PD-1/CTLA-4 | Nivolumab + Ipilimumab | Advanced Metastatic CRC | 2021 | Phase I | Active, not recruiting | / | |
| NCT03274804 | PD-1 | Pembrolizumab | MSS Metastatic CRC | 2017 | Phase I | Completed | A total of 20 patients with MSS CRC received a pembrolizumab plus maraviroc treatment. After the core treatment period of 8 cycles, the DCR and ORR were both 5.3%. Median PFS was 9 weeks (95% CI, from 7.0 to 10.0), and median OS was 9 months (95% CI, from 6.0 to 20.0). | ||
| NCT03711058 | PI3K | Copanlisib | PD-1 | Nivolumab | MSS Metastatic CRC | 2018 | Phase I/II | Active, not recruiting | / |
| NCT02646748 | PI3K-delta | INCB050465 | PD-1 | Pembrolizumab | Advanced Solid Tumors (CRC) | 2016 | Phase I | Completed | Not available |
| NCT05205330 | PGE2 | CR6086 | PD-1 | AGEN2034 | pMMR-MSS Metastatic CRC | 2022 | Phase Ib/IIa | Recruiting | / |
| NCT03658772 | PGE2-receptor/EP4 | Grapiprant | PD-1 | Pembrolizumab | MSS CRC | 2018 | Phase I | Active, not recruiting | / |
| NCT04432857 | AN0025 | PD-1 | Pembrolizumab | Advanced Solid Tumors (MSS CRC) | 2020 | Phase Ib | Recruiting | / | |
| NCT05205330 | CR6086 | PD-1 | AGEN2034 /Balstilimab | pMMR-MSS Metastatic CRC | 2022 | Phase Ib/IIa | Recruiting | / | |
| NCT04344795 | EP2/EP4 | TPST-1495 | PD-1 | Pembrolizumab | Solid Tumors (CRC) | 2020 | Phase Ia/Ib | Recruiting | / |
| NCT03026140 | COX2 | Celecoxib | PD-1/CTLA-4 | Nivolumab/Ipilimumab | Early-Stage Colon Cancer | 2017 | Phase II | Recruiting | / |
| NCT03926338 | Celecoxib | PD-L1 | Toripalimab | CRC | 2019 | Phase I/II | Recruiting | / | |
| NCT03638297 | COX | aspirin | PD-1 | BAT1306/pembrolizumab | MSI-H/dMMR Colorectal Cancer | 2018 | Phase II | Unknown | / |
| NCT02903914 | Arginase | INCB001158/CB-1158 | PD-1 | Pembrolizumab | Advanced/Metastatic Solid Tumors (CRC) | 2016 | Phase I/II | Active, not recruiting | / |
| NCT03436563 | TGF-βRII | M7824 | PD-L1 | M7824 | CRC | 2018 | Phase Ib/II | Active, not recruiting | / |
| NCT02947165 | TGF-β | NIS793 | PD-1 | PDR001 | Advanced Malignancies (CRC) | 2016 | Phase I/Ib | Completed | Not available |
| NCT04429542 | EGFR + TGF-β | BCA101 | PD-1 | Pembrolizumab | EGFR-driven Advanced Solid Tumors (CRC) | 2020 | Phase I | Recruiting | / |
| NCT04166383 | TNF-α | VB-111 | PD-1 | Nivolumab | Metastatic CRC | 2019 | Phase II | Active, not recruiting | / |
| NCT04060342 | CD11b | GB1275 | PD-1 | Pembrolizumab | MSS CRC | 2019 | Phase I | Terminated | / |
SD: stable disease; ORR: objective-response rate; DCR: disease-control rate.