Table 2. Selected immune-therapy clinical trials for Merkel cell carcinoma.
Therapies in the order listed in table: Avelumab= anti-PD-L1 (IgG1); Pembrolizumab= anti-PD-1 (IgG4); Nivolumab= anti-PD-1 (IgG4); Ipilimumab= anti-CTLA-4; GLA-SE= Glucopyranosyl Lipid A in Stable Emulsion, a TLR-4 agonist; F16-IL= Anti-tenascin C monoclonal antibody-interleukin 2 fusion protein; IL-12-EP= interleukin 12 plasmid administered with electroporation; MHC upregulation via through radiation or intratumoral Interferon ß administration; ALT-803=Interleukin 15 super-agonist complex; NK-92= activated, irradiated, allogenic natural killer cells; Bevacizumab= anti-VEGF; T-VEC=Talimogene laherparepvec, an engineered herpes oncolytic virus
| NCT identifier | Trial Arms | Recruitment Status | Phase | Targeted enrollment | Comments | Publications |
|---|---|---|---|---|---|---|
| Anti-PD-1/PD-L1 monotherapy | ||||||
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| NCT02155647 | Avelumab as ≥2nd line | Active not recruiting | II | 88 | 28 of 88 Chemotherapy-refractory patients achieved a response including 8 complete responses (ORR=32%) | Kaufman, 2016 (Kaufman, Lancet Oncol, 2016) |
| NCT02155647 | Avelumab as 1st line | Recruiting | II | 112 | Preliminary results show an objective response in 20 of 29 patients (ORR=69%) | D'Angelo, 2017 (D'Angelo, ASCO, 2017) |
| NCT02267603 | Pembrolizumab as 1st line | Active, not recruiting | II | 50 | 4 of 25 patients evaluated had a complete response and 10/25 had a partial response (ORR=56%) | Nghiem, 2016 (Nghiem, NEJM, 2016) |
| NCT02488759 | Nivolumab as 1st or ≥2nd line | Active, not recruiting | I/II | 25 | 22 patients initially evaluated on nivolumab alone, 12 had a partial response and 3 had a complete response (ORR=68%) | Topalian, 2017 (Topalian, AACR, 2017) |
| NCT02196961 | Avelumab as Adjuvant versus observation following resection | Recruiting | II | 113 | Only in Europea | |
| NCT03271372 | Avelumab as Adjuvant 1st line | Not yet recruiting | III | 100 | Stage III/IIIB nodal disease, randomized, double blinded | |
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| Checkpoint blockade combination therapy | ||||||
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| NCT02488759 | Nivolumab ± anti-LAG3 (BMS-9861016) ± Ipilimumab (many arms) | Recruiting | I/II | 500 | Cohort of patients with virus associated cancers | |
| NCT03071406 | Ipilimumab + nivolumab, Versus ipilimumab + nivolumab + stereotactic body radiation therapy | Recruiting | II | 50 | ||
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| Innate immunity agents & cytokines | ||||||
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| NCT02035657 | TLR-4 agonist, GLA-SE | Completed | I | 10 | 2 of 3 patients with local nodal disease had a complete response and 2 of 7 patients with distant metastatic disease had stable disease | Bhatia, 2016 (Bhatia, ASCO, 2016) |
| NCT01440816 | IL-12-EP | Completed | II | 15 | 4 of15 patients treated with IL-12 had an objective response | Bhatia, 2015 (Bhatia, ECC, 2015) |
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| Cell based therapies | ||||||
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| NCT02584829 | Autologous MCPyV specific CD8 cells + avelumab + MHC upregulation Versus avelumab + MHC upregulation | Recruiting | I/II | 20 | 4 of4 patients had responses with 3/4 complete responses | Paulson, 2017 (Paulson, ASCO, 2017) |
| NCT02465957 | NK cells (activated NK-92) + ALT-803 (modified IL-15) | Closed | II | 24 | Initial 3 patients showed no major toxicities and at least one patient had a response | Bhatia, 2016 (Bhatia, SITC, 2016) |
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| Oncolytic virus therapies | ||||||
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| NCT02819843 | T-VEC Versus T-VEC + hypofractionated radiotherapy | Recruiting | II | 34 | Cohort of melanoma and Merkel cell carcinoma | |
| NCT02978625 | T-VEC + nivolumab | Not yet recruiting | II | 68 | Cohort of refractory lymphomas and refractory non-melanoma skin cancers | |
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| Biomarker-guided combination therapy | ||||||
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| NCT03167164 | Avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, stereotactic body radiation therapy, ALT-803, NK-92 (many arms) | Not yet recruiting | I/II | 67 | Treatment customized based on tumor specific characteristics | |
a
unless otherwise noted, trials include sites within the US