Table 2:
Clinical trials of combined therapy using cetuximab and immunotherapy
| Study | Phase | Eligible Patients | Arms | Mechanism of Immunomodulator |
Enrollment | Main Outcome(s) |
Coordinating Institution |
Sponsor | Status |
|---|---|---|---|---|---|---|---|---|---|
| NCT01040832 | 2 | R/M HNSCC failing 1st line cytotoxic therapy | Cetuximab + EMD 1201081 Cetuximab alone | TLR-9 agonist | 107 (actual) | PFS | Multiple | EMD Serono | Completed. Ruzsa et al. |
| NCT01334177 | 1 | R/M HNSCC failing platinum or incurable with surgery or RT | Cetuximab + VTX-2337 | TLR-8 agonist | 13 (actual) | DLT, characterization of immunologic response | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | University of Washington | Completed. Dietsch et al. |
| NCT01360827 | 1 | R/M HNSCC not curable locally and not yet treated with systemic therapy or RT | EMD 1201081 + 5-FU + Cisplatin + Cetuximab | TLR-9 agonist | 13 (actual) | MTD, ORR | Clinical Research Unit and Pharmacology Lab EA 3035 Institut Claudius Regaud, Toulouse, France | Merck | Terminated due to safety concerns in combination with platinum-based therapy |
| NCT01468896 | 1, 2 | Unresectable R/M HNSCC | Cetuximab + recombinant IL-12 | IL-12 | 23 (actual) | DLT, ORR | MedStar Georgetown University Hospital | National Cancer Institute | Active. 2/23 DLT events. |
| NCT01836029 | 2 | R/M HNSCC not yet treated with systemic therapy | Cisplatin or carboplatin + 5-FU + cetuximab
+ VTX-2337 Cisplatin or carboplatin + 5-FU + cetuximab + placebo |
TLR-8 agonist | 175 (estimated) | PFS | Multiple | VentiRx Pharmaceuticals | Active |
| NCT01935921 | 1 | Locoregionally advanced HNSCC | Cetuximab + RT + ipilimumab | anti-CTLA4 | 19 (actual) | DLT, ORR | University of Pittsburgh Cancer Institute | National Cancer Institute | Completed. Ferris et al. |
| NCT02110082 | 1 | Advanced/metastatic CRC and incurable HNSCC | Cetuximab + urelumab | anti-CD 137 | 66 (actual) | Toxicities Objective response rate | Multiple | Bristol-Myers Squibb | Completed. Results pending. |
| NCT02124850 | 1 | Resectable primary HNSCC | Surgery + cetuximab + motolimod
Surgery + cetuximab + motolimod + nivolumab |
TLR-8 agonist (motolimod) anti-PD-1 Mab (nivolumab) | 24 (estimated) | Change in immune markers anti-tumor response | University of Pittsburgh Medical Center | VentiRx Pharmaceuticals | Recruiting |
| NCT02633800 | 2 | R/M HNSCC not previously treated with systemic therapy | Cetuximab + platinum +
patritumab Cetuximab + platinum + placebo |
anti-HER3 Mab | 87 (actual) | PFS | Multiple | Daiichi Sankyo, Inc. | Completed. Results submitted. |
| NCT02643550 | 1, 2 | Platinum-resistant R/M HNSCC | Cetuximab + monalizumab | anti-NKG2A Mab | 100 (estimated) | DLT, ORR | University of Pennsylvania | Innate Pharma | Recruiting |
| NCT02764593 | 1 | Locoregionally advanced HNSCC | Nivolumab + cisplatin Nivolumab + high dose cisplatin Nivolumab + cetuximab Nivolumab + IMRT |
anti-PD-1 Mab | 40 (actual) | DLT | Multiple | Radiation Therapy Oncology Group, Bristol-Myers Squibb | Active |
| NCT02938273 | 1 | New diagnosis locally advanced HNSCC | RT + cetuximab + avelumab | anti-PD-L1 Mab | 10 (estimated) | Grade 3-5 toxicity Overall response rate | The Netherlands Cancer Institute | Merck | Recruiting |
| NCT02999087 | 3 | Untreated locoregionally advanced HNSCC | RT + cisplatin RT + cetuximab + avelumab RT + cetuximab |
anti-PD-L1 Mab | 688 (estimated) | PFS | Centre Hospitalier Bretagne Sud, Lorient, France | Groupe Oncologie Radiotherapie Tete et Cou, Merck, Pfizer | Recruiting |
| NCT03051906 | 1, 2 | Locoregionally advanced HNSCC | RT + cetuximab + durvalumab | anti-PD-L1 Mab | 69 (estimated) | PFS | Azienda Ospedaliero-Universitaria Careggi | Azienda Ospedaliero-Universitaria Careggi | Not yet recruiting. Bonomo et al. |
| NCT03082534 | 2 | Incurable platinum-refratory or ineligibile HNSCC | Cetuximab + pembrolizumab | anti-PD-1 Mab | 83 (estimated) | ORR | UC San Diego Moores Cancer Center | Merck Sharp & Dohme Corp. | Recruiting |
| NCT03349710 | 3 | R/M HNSCC not curable locally and not yet treated with systemic therapy or RT | Cetuximab + nivolumab + RT Cetuximab + placebo + RT Nivolumab + cisplatin + RT Placebo + cisplatin + RT |
anti-PD-1 Mab | 1,046 (estimated) | PFS | Multiple | Bristol-Myers Squibb | Recruiting |
| NCT03370276 | 1, 2 | incurable R/M HNSCC | Cetuximab + nivolumab | anti-PD-1 Mab | 52 (estimated) | MTD, 1-year OS | H. Lee Moffitt Cancer Center and Research Institute | H. Lee Moffitt Cancer Center and Research Institute, Bristol-Myers Squibb, Eli Lilly and Company | Active |
| NCT03494322 | 2 | Incurable R/M HNSCC | Cetuximab + avelumab Avelumab alone |
anti-PD-L1 Mab | 130 (estimated) | DLT, ORR | University College, London | Merck | Recruiting |
| NCT03498378 | 1 | Incurable HNSCC | Cetuximab + avelumab + palbociclib | anti-PD-L1 Mab(avelumab) CDK4 and CDK6 inhibitor (palbociclib) | 24 (estimated) | MTD, ORR | UC San Diego Moores Cancer Center | Pfizer | Recruiting |
| NCT01860430 | 1 | Locoregionally advanced HNSCC | Cetuximab + IMRT + ipilimumab | anti-CTLA4 | 18 (estimated) | Dosing, ORR | University of Pittsburgh Cancer Institute | National Cancer Institute, Robert Ferris | Active |
Abbreviations: CRC (colorectal cancer), DLT (dose-limiting toxicities), HNSCC (head and neck squamous cell carcinoma), MTD (maximum tolerated dose), ORR (objective response rate), PFS (progression free survival), R/M (recurrent or metastatic), RT (radiotherapy)