Table 2.
Ongoing trials investigating immune checkpoint blockade (ICB) in advanced cSCC.
| Study ID | Study Design | Start | End * | Sample Size [n] | Intervention | Primary Outcomes | Secondary Outcomes | Funding |
|---|---|---|---|---|---|---|---|---|
| NCT03901573 | Multicenter, open-label, phase Ib | Dec 2019 | May 2024 | 24 | Atezolizumab i.v.+ efineptakin alfa (hIL-7-hyFc) i.m. Dose escalation |
Safety and tolerability | ORR, DCR, DOR, PFS, OS | NeoImmuneTech Immune Oncology Network |
| Multicenter, open-label, two armed, phase IIa | 60 (A = 24, B = 36) |
Atezolizumab i.v.+ efineptakin alfa (rhIL-7-hyFc) i.m. A: ICB-refractory cSCC B: ICB-naïve cSCC Dose expansion |
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| NCT03108131 | Single-center, single-arm, open-label, phase II | Apr 2017 | Jul 2020 | 60 | Atezolizumab i.v. Q2W + cobimetinib p.o. QD on days 1–12, 1 cycle = 28 days, until disease progression or unacceptable toxicity | ORR | PFS | M.D. Anderson Cancer Center National Cancer Institute (NCI) |
| NCT03944941 | Multicenter, open-label, randomized, two-armed, phase II | May 2019 | Dec 2023 | 59 | A: Avelumab i.v. on days 1 and 15, up to 24 cycles (1 cycle = 28 days), until disease progression or unacceptable toxicity; patients with avelumab failure will crossover to arm B B: Avelumab + cetuximab: and avelumab i.v. on days 1 and 15 + cetuximab i.v. on days 1, 8, 15, and 22, up to 24 cycles until disease progression or unacceptable toxicity |
PFS | ORR, clinical benefit rate, OS, AEs | Alliance for Clinical Trials in Oncology National Cancer Institute (NCI) |
| AliCe Trial EudraCT: 2018-001708-12 |
Multicenter, open-label, single-arm, phase II | un-clear | un-clear | 52 | Avelumab i.v. + cetuximab i.v., intervals and dosage not reported | ORR | PFS, DOR, OS, AEs, QoL | Alcedis GmbH |
| UNSCARRed trial NCT03737721 |
Single-center, single-arm, open-label, phase II | Apr 2019 | Jun 2023 | 20 | Avelumab i.v. Q2W, first dose 14 days prior to radiotherapy, then 63–66 Gy radiation over 30 daily fractions + avelumab i.v. Q2W for 4 cycles | ORR | PFS, clinical and pathological response rate, AEs | AHS Cancer Control Alberta EMD Serono Alberta Cancer Foundation |
| NCT03889912 | Multicenter, single-arm, open-label, phase I | Apr 2019 | Feb 2022 | 36 | Cemiplimab i.t. QW for 12 weeks neoadjuvant, then surgical excision | AEs | ORR, CR rate, pathological response rate, drug concentration over time, anti-drug antibodies | Regeneron Pharmaceuticals Sanofi |
| NCT04154943 | Multicenter, single-arm, open-label, phase II | Mar 2020 | Dec 2024 | 76 | Cemiplimab i.v. Q3W | Pathologic CR rate | Major pathologic response, ORR, event-free survival, DFS, OS, AEs, incidence of deaths | Regeneron Pharmaceuticals Sanofi |
|
NCT03969004 (EudraCT: 2019-000566-38) |
Randomized, multicenter, two-armed, double-blind, phase III | Jun 2019 | Feb 2026 | 412 | Surgery and radiation therapy followed by A: Cemiplimab i.v. B: Placebo i.v. Intervals and dosage not reported |
DFS | OS, freedom from locoregional and distant recurrence, cumulative occurance of second primary cSCC, AEs, incidence of deaths | Regeneron Pharmaceuticals Sanofi |
| NCT04242173 | Single-center, single-arm, open-label, phase II | Jan 2020 | Jan 2023 | 27 | Cemiplimab i.v., intervals and dosage not reported | ORR | PFS, OS | Regeneron Pharmaceuticals Sanofi |
| CERPASS trial NCT04050436 |
Randomized, multicenter, two-armed, open-label, phase II | Oct 2019 | Mar 2024 | 240 | A: Cemiplimab i.v. Q3W B: Cemiplimab i.v. Q3W+ RP1 i.t. Q3W |
ORR | DOR, PFS, CR rate, OS, AEs, response injected vs. non-injected lesions | Replimune Inc. Regeneron Pharmaceuticals |
| CONTRAC trial NCT04339062 |
Non-randomized, single-center, open-label, phase I | Jul 2020 | Jul 2022 | 12 A: allo-HCT B: kidney trans-plant reci-pients |
A: Cemiplimab i.v. Q3W B: Cemiplimab i.v. Q3W + everolimus/sirolimus 7–10 days prior to cemiplimab start, then QD + prednisone 40 mg p.o. 1 day prior to cemiplimab start, then QD at tapering doses |
Dose-limiting toxicity (A: GVHD, B: allograft rejection) | PFS, OS, ORR, therapeutic response rate, secondary infection rate, | Dana-Farber Cancer Institute Regeneron Pharmaceuticals |
|
NCT02760498 (EudraCT: 2016-000105-36) |
Multicenter, open-label, phase II | Apr 2016 | Dec 2025 | 433 | Cemiplimab i.v. A: mSCC, Q2W B: laSCC, Q2W C: mSCC, Q3W D: mSCC or laSCC, Q4W E: mSCC or laSCC, Q3W |
ORR | DoR, PFS, OS, CR rate, QoL, AEs, pharmacokinetics, correlation PD-L1 expression and ORR/DoR/PFS | Regeneron Pharmaceuticals |
| NCT04428671 | Single-center, open-label, phase I | May 2020 | Oct 2030 | 20 | Cemiplimab i.v. Q3W neoadjuvant for up to 3 cycles prior to surgery, then cemiplimab i.v. Q3W adjuvant, starting within 2–6 weeks after surgery or radiation therapy, up to 18 cycles | Pathologic RR | Time to local and systemic recurrence, OS, RFS | Emory University |
| NCT04315701 | Multicenter, open-label, phase II | Jun 2020 | Jan 2023 | 34 | Cemiplimab i.v. Q3W up to 3 cycles neoadjuvant, then surgery within 6 weeks after last dose | Pathologic PR | Pathologic CR rate, ORR, PFS, AEs | M.D. Anderson Cancer Center National Cancer Institute (NCI) |
| NCT03684785 | Multicenter, open-label, phase Ib | Dec 2018 | Jun 2023 | 130 | Cavrotolimod i.t. twice (dosage and intervals not reported), then with pembrolizumab 2 mg/kg i.v. Q3W Dose escalation |
AEs | Finding recommended dose of cavrotolimod for phase II trial ORR, biomarkers |
Exicure, Inc. |
| Phase II | Cemiplimab 350 mg i.v. Q3W + cavrotolimod i.t. Dose expansion |
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| NCT04305795 | Open-label, phase I/II | Sep 2020 | Jun 2024 | 54 | Cemiplimab 350 mg i.v., up to 24 months + ASP-1929 (EGFR antibody-dye conjugate for photoimmunotherapy light treatment) |
AEs, ORR | OS, PFS, DOR | Rakuten Medical, Inc. |
| NCT03816332 | Multicenter, single-arm, open-label, phase I | Feb 2019 | May 2021 | 16 kidney trans-plant reci-pients |
Tacrolimus p.o. BID + prednisone p.o. QD, within 28 days: Nivolumab i.v. Q4W, up to 24 cycles until disease progression or unacceptable toxicity. Patients with PD at 16 weeks: Nivolumab i.v. + ipilimumab i.v. Q3W + tacrolimus p.o. BID + prednisone p.o. QD, up to 4 cycles until disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab i.v. Q4W, up to 21 cycles until disease progression or unacceptable toxicity. |
CR, PR and SD rate, patients without allograft loss | ORR, allograft rejection rate, DOR (CR and PR), PFS, OS | National Cancer Institute (NCI) |
| CA209-9JC trial NCT03834233 |
Single-center, open-label, phase II | Sep 2019 | Dec 2022 | 24 | Nivolumab 3 mg/kg i.v. Q2W until disease progression or up to 12 months | ORR | AEs, PFS | Instituto do Cancer do Estado de São Paulo |
| NCT04204837 | Multicenter, open-label, phase II | Mar 2017 | Dec 2023 | 31 | Nivolumab 240 mg i.v. Q2W until disease progression, unacceptable toxicity or up to 2 years | ORR | DCR, DOR, PFS, OS | Salzburger Landeskliniken Bristol-Myers Squibb |
| NCT02978625 | Multicenter, open-label, phase II | Sep 2017 | Jun 2021 | 68 | T-VEC i.t. on day 1, if no response: Nivolumab i.v. Q3W (first cycle), then Q2W until disease progression, unacceptable toxicity or up to 1 year |
RR to T-VEC alone, ORR to T-VEC + nivolumab | Durable RR, RR of injected and non-injected lesions, PFS, OS, AEs | National Cancer Institute (NCI) |
| Pelican trial NCT03773744 |
Open-label, phase I | Jan 2020 | Dec 2021 | 40 | A: Cyclophosphamide 300mg/m2 3 days prior to Ad-MAGEA3 fixed dose i.m. (day 1), then one of 3 dose levels of MG1-MAGEA3 i.v. (day 15 and 18) + pembrolizumab 200 mg i.v., starting in week 6 or on day 1 (depending on cohort; intervals not reported) B: Ad-MAGEA3 fixed dose i.m. followed by pembrolizumab i.v. (day 1), then MG1-MAGEA3 i.v. (day 15) and i.t. on day 22, 29, and 36; MG1-MAGEA3 booster injections i.t. Q3W beginning at day 43 (=week 6) |
AEs, maximum tolerated and feasible dose of Ad/MG-MAGEA3 | ORR, DCR, PFS, DOR | Turnstone Biologics, Corp. |
| KEYNOTE-629 NCT03284424 (EudraCT: 2017-000594-37) |
Multicenter, two-armed, open-label, phase II | Oct 2017 | Jun 2022 | 150 | Pembrolizumab 200 mg i.v. Q3W up to 2 years A: recurrent or mSCC B: laSCC |
ORR | DOR, DCR, PFS, OS, AEs, discontinuations due to AEs | Merck Sharp & Dohme Corp. |
| KEYNOTE-630 NCT03833167 (EudraCT: 2018-001974-76) |
Randomized, multicenter, blinded, controlled, phase III | Apr 2019 | Sep 2027 | 570 | Adjuvant setting A: Pembrolizumab 400 mg i.v. Q6W, up to 9 cycles; if 9 cycles completed: Up to 18 additional cycles in open-label design B: Placebo i.v. Q6W, up to 9 cycles; if disease recurrence: Up to 18 cycles of pembrolizumab in open-label design |
RFS | OS, QoL, AEs, discontinuations due to AEs | Merck Sharp & Dohme Corp. |
| NCT02964559 | Single-center, open-label, phase II | Jan 2017 | Feb 2022 | 11 | Pembrolizumab i.v. Q3W until disease progression or unacceptable toxicity | RR | OS, PFS | Emory University Merck Sharp & Dohme Corp. |
| CARSKIN trial NCT02883556 (EudraCT: 2016-002076-28) |
Single-center, open-label, phase II | Mar 2017 | Oct 2021 | 57 | Pembrolizumab 200 mg i.v. Q3W until disease progression or unacceptable toxicity, or up to 24 months | RR | AEs, RR in PD-L1 positive patients, DCR, OS, PFS, DOR, duration of control, time to progression | Assistance Publique - Hôpitaux de Paris |
| NCT02721732 | Single-center, open-label, phase II | Aug 2016 | Aug 2020 | 225 | Pembrolizumab i.v. Q3W until disease progression or unacceptable toxicity, or up to 24 months; responding patients may continue up to 12 additional months | Non-progression rate, AEs | ORR, clinical benefit (CR, PR or SD), DOR, PFS, OS, ECOG performance status, temperature, pulse, body weight, respiratory rate, blood pressure | M.D. Anderson Cancer Center National Cancer Institute (NCI) |
| NCT04234113 | Multicenter, open-label, phase I | Jun 2019 | Mar 2022 | 96 | A: SO-C101 (IL-15 agonist) B: SO-C101 + Pembrolizumab i.v. unclear dosing and intervals |
Dose-limiting toxicity, AEs, laboratory test abnormalities, ECOG performance status | ORR, best overall response, DOR, clinical benefit rate, PFS, anti-drug antibodies to SO-C101 | Sotio a.s. |
*: estimated; Abbreviations: Ad-MAGEA3: Adenovirus vaccine expressing Melanoma-associated antigen 3, AEs: adverse events, allo-HCT: allogeneic hematopoietic stem cell transplant, BID: twice daily, CR: complete response, cSCC: cutaneous squamous cell carcinoma, DCR: disease control rate, DOR: Duration of response, GVHD: Graft-versus-Host-disease, Gy: Gray, i.m.: intramuscular, i.t.: intratumoral, i.v.: intravenous, laSCC: locally advanced cSCC, MG1-MAGEA3: MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3, mSCC: metastatic cSCC, ORR: objective response rate, OS: Overall survival, PFS: Progression-free survival, p.o.: per os, PR: partial response, QoL: quality of life, QD: daily, QW: every week, Q2W: every 2 weeks, Q3W: every 3 weeks, Q4W: every 4 weeks, Q6W: every 6 weeks, RFS: recurrence free survival, RR: response rate, rhIL-7-hyFc: recombinant human interleukin-7 and hybrid Fc fusion protein, RP1: genetically modified herpes simplex virus 1; T-VEC: Talimogene laherparepvec.