Table 1.
Emerging Studies and Novel Approaches to the Treatment of Metastatic Anal Cancer8,21,23,25,32,34,36–40
| Trial Short Name | NCT Identifier | Phase | Line of Therapy | Treatment Arms | Description |
|---|---|---|---|---|---|
| NCI 9673, Part A | NCT02314169 | 2 | Refractory | Nivolumab 3 mg/kg every two weeks | PD-1 inhibitor with CTLA-4 inhibitor Primary Endpoint, ORR: 24% Secondary Endpoints -Median PFS: 4.1 months (95% CI, 3.0 to 7.9) -Median OS: 11.5 months (95% CI, 7.1 to NE) |
| NCI 9673, Part B | NCT02314169 | 2 | Refractory | Nivolumab 480 mg IV every four weeks Nivolumab 480 mg IV every 4 weeks + Ipilimumab 1 mg/kg IV every 8 weeks |
PD-1 inhibitor with CTLA-4 inhibitor Results pending |
| KEYNOTE-158 | NCT02628067 | 2 | Refractory | Pembrolizumab 200 mg IV every 3 weeks | PD-1 inhibitor Primary Endpoint, ORR: 11.6% (95% CI, 6.3 to 19.0) Secondary Endpoints -Median PFS: 2.0 months (95% CI, 2.0 to 2.1) -Median OS: 12.0 months (95% CI, 9.1 to 15.4) |
| POD1UM-202 | NCT03597295 | 2 | Refractory | Retifanlimab 500 mg IV every 4 weeks | PD-1 inhibitor Primary Endpoint, ORR: 13.8% Secondary Endpoints -Median PFS: 2.3 months (95% CI, 1.9 to 3.6) -Median OS: 10.1 months (95% CI, 7.9 to NE) |
| NCT03074513 | NCT03074513 | 2 | Refractory | Atezolizumab 1200 mg IV + bevacizumab 15 mg/kg IV every 3 weeks | PD-L1 inhibitor with VEGF inhibitor Primary Endpoint, ORR: 10% (95% CI, 1.2 to 32) Secondary Endpoints -Median PFS: 4.1 months (95% CI, 2.6 to NE) -Median OS: 11.6 months (95% CI, 9.5 to 20) |
| CARACAS | NCT03944252 | 2 | Refractory | Avelumab 10 mg/kg IV every 2 weeks Avelumab 10 mg/kg IV + cetuximab 500 mg/m2 IV every 2 weeks |
PD-L1 inhibitor ± EGFR inhibitor Primary Endpoint, ORR: 10% (95% CI, 2.1 to 26.5%) vs 17% (95% CI, 5.6 to 34.7) Secondary Endpoints -Median PFS: 2.0 months (95% CI, 1.8 to 4.0) vs 3.9 (95% CI, 2.1 to 5.6) -Median OS: 13.9 months (95% CI, 7.7 to 19.4) vs 7.8 (95% CI, 6.2 to 11.2) |
| BCA101X1101 | NCT04429542 | 1/1b | Cohort Dependent | BCA101 IV weekly + Pembrolizumab 200 mg IV every three weeks | EGFR/TGFβ bifunctional fusion antibody ± PD-1 inhibitor Dose escalation and dose expansion study design Results pending |
| NKTR-255 | NCT04616196 | 1b/2 | Cohort Dependent | NKTR-255 IV every three weeks + Cetuximab | IL-15 agonist with EGFR inhibitor Results pending |
| ADXS001-0637 | NCT02399813 | 2 | Refractory | ADXS11-001 1×109 CFU IV every three weeks | Antigen-adjuvant fusion protein of Lysteriolysin O and HPV-16 E7 Primary Endpoint, ORR: 3.4% Study failed to meet the primary endpoint of ORR of 10% |
| NCI-2015-0100438 | NCT02426892 | 2 | Refractory | ISA101 100 mcg/peptide SQ every three weeks x3 doses + Nivolumab 3 mg/kg IV Q2W | HPV-16 vaccine with PD-1 inhibitor Anal cancer (n=1) |
| NCI-2018-0091439 | NCT03439085 | 2 | Refractory | MEDI0457 7 mg IM Q2-4W x4 doses then Q8W + Durvalumab 1500 mg IV Q4W | HPV 16/18 vaccine with PD-L1 inhibitor Primary Endpoint, ORR: 21% (95% CI, 6 to 46%) Secondary Endpoints -Median PFS: 3.7 months (95% CI, 2.8 to 9.2) -Median OS:13.5 months (95% CI, 10.1 to NE) |
| Future Steps | |||||
| InterAACT2 / POD1UM-30340 |
NCT04472429 | 3 | Front-Line | Carboplatin AUC 5 IV every 4 weeks + Paclitaxel 80 mg/m2 IV weekly x3 doses + Placebo (28 day cycles) Carboplatin+Paclitaxel + Retifanlimab 500 mg IV every 4 weeks |
PD-1 inhibitor or placebo + chemotherapy |
| EA217642 | NCT04444921 | 3 | Front-Line | Carboplatin AUC 5 IV every 4 weeks + Paclitaxel 80 mg/m2 IV weekly x3 doses + Nivolumab 480 mg IV (28 day cycles) | PD-1 inhibitor or placebo + chemotherapy |
| SCARCE43 | NCT03519295 | 2 | Front-Line | mDCF Q2W x8 cycles + Placebo x8 cycles mDCF Q2W x8 cycles + Atezolizumab 800 mg IV Q2W x24 cycles |
PD-L1 inhibitor or placebo + chemotherapy Primary Endpoint, 12-month PFS rate Secondary Endpoints: PFS, OS, response rate, safety |
| SPARTANA | NCT04894370 | 2 | Front-Line | Modified DCF + Spartalizumab Spartalizumab maintenance |
Multimodality approach involving ablative therapies, radiotherapy, and chemoimmunotherapy |
| NCI 20-C-004557 | NCT04287868 | 1/2 | Refractory | PDS0101 1 mL SQ every 2 weeks x3, then every 4 weeks + M7824 1200 mg IV every 2 weeks + NHS-IL12 SQ every 4 weeks | HPV vaccine with bifunctional PD-L1/TGFβ fusion protein with IL-agonist triple therapy |
| VolATIL59 | NCT03946358 | 2 | Refractory | UCPVax 1 mg SQ weekly x6 doses then five boosters given every 6–9 weeks + Atezolizumab 1200 mg IV every 3 weeks | CD4 helper T-inducer cancer vaccine with PD-L1 inhibitor |
| Ad-MG1-E6E7-00260 | NCT03618953 | 1 | Refractory | MG1-E6E7 + Ad-E6E7 + Atezolizumab 1200 mg IV every 3 weeks | HPV vaccine with PD-L1 inhibitor |
| SQZ-PBMC-HPV-10161 | NCT04084951 | 1 | Refractory | SQZ-PBMC-HPV alone or with atezolizumab | Selected for HLA-A*02 patients with HPV16 positive tumors |
Abbreviations: PD-1, programmed death-1; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; ORR, overall response rate; PFS, progression-free survival; OS, overall survival; NE, not evaluable; PD-L1, programmed death ligand-1; VEGF, vascular endothelial growth factor; EGFR, epidermal growth factor receptor; TGFβ, transforming growth factor beta; IL-15, interleukin-15; HPV, human papillomavirus; mDCF, modified docetaxel + cisplatin + 5-Fluorouracil.