Table 1.
Clinical trials incorporating checkpoint inhibitors and radiation therapy in head and neck squamous cell carcinoma.
| NCT ID# | Phase | Title | ICI | Treatment arms |
|---|---|---|---|---|
| PHASE 1 | ||||
| NCT03539198 | NA | A prospective observational study of study of proton SBRT and immunotherapy for recurrent/progressive locoregional or metastatic head and neck cancer | Nivolumab | Loading dose of Nivolumab on D-14 then concurrently w/RT; Proton SBRT 5 fxs; 35–45 Gy) |
| NCT02764593 | 1 | Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer | Nivolumab | Loading dose on D-14 then concurrently w/cisplatin or cetuximab and RT, followed by adjuvant ICI; 70 Gy in 35 fxs; IMRT |
| NCT03402737 | 1 | SBRT + Immunomodulating Systemic Therapy for Inoperable, Recurrent Head and Neck Cancer | Nivolumab | Concurrently w/RT; 6–8 Gy times 2 fxs 6–8 Gy times 3 fxs 6–10 Gy times 3 fxs 6–12 Gy times 3 fxs |
| NCT02318771 | 1 | Radiation therapy and MK-3475 for patients with recurrent/metastatic head and neck cancer, renal cell cancer, melanoma, and lung cancer | Pembrolizumab | Arm A: Adjuvant (3–17 days post RT); Arm B: Concurrent; A1 and B1: 8 Gy in 1 fx Arms A2 and B2: 20 Gy in 5 fxs |
| NCT02586207 | 1 | Pembrolizumab in combination with CRT for LA-SCCHN | Pembrolizumab | Loading dose on D-7 then concurrent q3 weeks with cisplatin-RT;70 Gy in 35 fxs |
| NCT02819752 | 1 | Pembrolizumab combined with chemoradiotherapy in squamous cell carcinoma of the head and neck (PEACH) | Pembrolizumab | Concurrently with CRT; Standard therapy |
| NCT03509012 | 1 | Immunotherapy in combination with chemoradiation in patients with advanced solid tumors (CLOVER) | Durvalumab | Various regimens |
| NCT02938273 | 1 | Bioimmunoradiotherapy (Cetuximab/RT/Avelumab) | Avelumab | Loading dose D-7 then concurrently w/cetuximab-RT; 70 Gy over 7 weeks |
| NCT01935921 | 1 | Ipilimumab, cetuximab, and intensity-modulated radiation therapy in treating patients with previously untreated stage III-IVB head and neck cancer | Ipilimumab | Concurrently w/cetuximab-RT; IMRT daily for 7 weeks |
| NCT01860430 | 1 | A phase Ib trial of concurrent cetuximab (ERBITUX®) and intensity modulated radiotherapy (IMRT) With ipilimumab (YERVOY®) in locally advanced head and neck cancer | Ipilimumab | Concurrently w/cetuximab-RT; 70–74 Gy in 2 Gy daily fxs; IMRT |
| NCT03162731 | 1 | Nivolumab, ipilimumab, and radiation therapy in treating patients with stage IVA-B head and neck cancer | Nivolumab, Ipilimumab | Loading dose of Nivolumab on D-21 then concurrently w/RT and ipilimumab; 70 Gy in 35 fxs |
| NCT03529422 | 1 | Durvalumab and Tremelimumab with radiotherapy for adjuvant treatment of intermediate risk SCCHN | Durvalumab, Tremelimumab | Concurrently w/RT; 60 Gy in 30 fxs; IMRT |
| NCT03317327 | 1/2 | REirradiation and programmed cell death protein 1 (PD-1) blockade on recurrent squamous cell head and neck tumors (REPORT) | Nivolumab | Concurrently w/RT; 60 Gy in 1.5 Gy fxs BID for 4 weeks |
| NCT03247712 | 1/2 | Neoadjuvant immunoradiotherapy in head and neck cancer | Nivolumab | Concurrently w/RT; Arm 1: 8 Gy times 5 fxs daily Arm 2: 8 Gy times 3 fxs QOD |
| NCT02759575 | 1/2 | A study of chemoradiation plus pembrolizumab for locally advanced laryngeal squamous cell carcinoma | Pembrolizumab | Loading dose on D-21 then concurrently w/cis-RT; 70 Gy in 35 fxs |
| NCT03114280 | 1/2 | Pembrolizumab and induction chemotherapy in head and neck squamous cell carcinoma (PICH study) (PICH) | Pembrolizumab | Neoadjuvant with chemotherapy, followed by concurrent chemoradiotherapy with carboplatin; Unknown dose or RT |
| NCT03051906 | 1/2 | Durvalumab, cetuximab, and radiotherapy in head neck cancer (DUCRO-HN) | Durvalumab | Concurrently w/cetuximab-RT followed by adjuvant therapy; 69.96 Gy in 2.12 Gy fxs |
| NCT03212469 | 1/2 | A trial of durvalumab and tremelimumab in combination with SBRT in patients with metastatic cancer (ABBIMUNE) | Durvalumab, tremelimumab | SBRT |
| NCT03283605 | 1/2 | Immunotherapy and SBRT for metastatic head and neck carcinomas | Durvalumab, tremelimumab | Neoadjuvant then concurrently w/RT; SBRT |
| NCT03522584 | 1/2 | Durvalumab, tremelimumab, and stereotactic body radiation therapy in treating participants with recurrent or metastatic head and neck squamous cell carcinoma | Durvalumab, tremelimumab | Loading dose D-14 then concurrently w/RT; SBRT QOD |
| PHASE 2 | ||||
| NCT02684253 | 2 | Screening trial of nivolumab with image guided, stereotactic body radiotherapy (SBRT) vs. nivolumab alone in patients with metastatic head and neck squamous cell carcinoma (HNSCC) | Nivolumab | Concurrently w/RT; SBRT 27 Gy in 3 fxs QOD |
| NCT03521570 | 2 | Intensity-modulated radiation therapy and nivolumab for recurrent or second primary head and neck squamous cell cancer | Nivolumab | Loading dose of Nivolumab on D-14 then concurrently with RT; IMRT daily for 6–6.5 weeks |
| NCT03107182 | 2 | Chemotherapy and locoregional therapy trial (surgery or radiation) for patients with head and neck cancer (OPTIMA-II) | Nivolumab | Induction with chemotherapy followed by adjuvant therapy; Dose de-escalated to 45–50 Gy (Arm 2 and 3) or conventional dose to 70 Gy (Arm 4) |
| NCT03511391 | 2 | Checkpoint inhibition in combination with an immunoboost of external body radiotherapy in solid tumors (CHEERS) | Pembrolizumab, Nivolumab | Concurrently with RT; SBRT 8 Gy times 3 fxs |
| NCT03313804 | 2 | Priming immunotherapy in advanced disease with radiation | Pembrolizumab, Nivolumab, Atezolizumab | Concurrently w/RT; SBRT with BED >100 Gy or 30 Gy in 3 Gy fxs |
| NCT02641093 | 2 | Phase II trial of adjuvant cisplatin and radiation with pembrolizumab in resected head and neck squamous cell carcinoma | Pembrolizumab | Loading dose 1 week prior to surgery then concurrently w/ cis-RT; 60–66 Gy in 2 Gy fxs |
| NCT02707588 | 2 | Tolerance and efficacy of pembrolizumab or cetuximab combined with RT in patients with locally advanced HNSCC (PembroRad) | Pembrolizumab | Concurrently w/RT; 69.96 Gy in 2.12 Gy daily fxs |
| NCT02609503 | 2 | Pembrolizumab + radiation for locally Adv SCC of the Head and Neck (SCCHN) Not eligible cisplatin | Pembrolizumab | Concurrently w/RT; IMRT daily for 7 weeks |
| NCT02296684 | 2 | Immunotherapy with MK-3475 in surgically resectable head and neck squamous cell carcinoma | Pembrolizumab | Arm 1: Neoadjuvant and adjuvant therapy Arm 2: Neoadjuvant; |
| NCT02289209 | 2 | Reirradiation With pembrolizumab in locoregional inoperable recurrence or second primary squamous cell CA of the head and neck | Pembrolizumab | Concurrently w/RT; 1.2 Gy BID for 5 days a week for 5 weeks |
| NCT02777385 | 2 | Pembrolizumab in combination with cisplatin and intensity modulated radiotherapy (IMRT) in head and neck cancer | Pembrolizumab | Arm 1: adjuvant 3 weeks post cisplatin-RT Arm 2: concurrently with cisplatin-RT; 70 Gy in 35 fxs; IMRT |
| NCT03085719 | 2 | Targeting PD-1 therapy resistance with focused high or high and low dose radiation in SCCHN | Pembrolizumab | Concurrently w/RT; High (3 fxs) vs. low dose (2 fxs) |
| NCT03532737 | 2 | Concomitant immune check point inhibitor with radiochemotherapy in head and neck cancer | Pembrolizumab | Loading dose on D-14 then concurrently w/either cetuximab or cis-RT; 66–70 Gy in 30–35 fxs; IMRT |
| NCT03057613 | 2 | The addition of pembrolizumab to postoperative radiotherapy in cutaneous squamous cell cancer of the head and neck | Pembrolizumab | Concurrently w/and adjuvantly to post-op RT; 60–66 Gy for 6 weeks; IMRT |
| NCT03383094 | 2 | Chemoradiation vs. immunotherapy and radiation for head and neck cancer | Pembrolizumab | Concurrently w/and adjuvant to cis-RT; 70 Gy in 33–35 fxs |
| NCT03546582 | 2 | SBRT +/– pembrolizumab in patients with local-regionally recurrent or second primary head and neck carcinoma (KEYSTROKE) | Pembrolizumab | Adjuvant to RT; SBRT |
| NCT03386357 | 2 | Radiotherapy with pembrolizumab in metastatic HNSCC | Pembrolizumab | Concurrently w/RT; 12 Gy times 3 fxs |
| NCT03624231 | 2 | Feasibility and efficacy of Durvalumab+Tremelimumab+RT and Durvalumab+RT in Non-resect. Locally advanced HPVnegativ HNSCC (DURTRE-RAD) | Durvalumab, Tremelimumab | Loading dose D-14 then concurrently w/ RT, followed by adjuvant therapy; 70 Gy in 35 fxs over 7 weeks |
| NCT03426657 | 2 | Radiotherapy with double checkpoint blockade of locally advanced HNSCC | Durvalumab, Tremelimumab | Concurrently w/RT followed by durva monotherapy; 70 Gy in 35 fxs |
| NCT03258554 | 2/3 | Radiation therapy with Durvalumab or Cetuximab in treating patients with stage III-IVB head and neck cancer who cannot take cisplatin | Durvalumab | Loading dose D-14 then concurrently w/RT; IMRT |
| PHASE 3 | ||||
| NCT03349710 (closed to slow accrual) | 3 | Nivolumab or nivolumab plus cisplatin, in combination WITH radiotherapy in patients with cisplatin-ineligible or eligible locally advanced squamous cell head and neck cancer | Nivolumab | RT w/cis and nivo vs. RT w/cis RT w/cetuximab vs. RT w/nivo 70 Gy in 35 fractions over 7 weeks; IMRT |
| NCT03576417 | 3 | A trial evaluating the addition of nivolumab to cisplatin-rt for treatment of cancers of the head and neck (NIVOPOSTOP) | Nivolumab | Loading dose of Nivolumab on D-21 then concurrently w/cis-RT; 66 Gy over 6.5 weeks; IMRT |
| NCT03040999 | 3 | Study of pembrolizumab (MK-3475) or placebo with chemoradiation in participants with locally advanced head and neck squamous cell carcinoma (MK-3475-412/KEYNOTE-412) | Pembrolizumab | Loading dose then concurrently w/cis-RT; 70 Gy in 35 fxs over either 6 (accelerated) or 7 (standard) weeks |
| NCT02952586 | 3 | Study to compare avelumab in combination with standard of care chemoradiotherapy (SoC CRT) vs. SoC CRT for definitive treatment in patients with locally advanced squamous cell carcinoma of the head and neck (Javelin head and neck 100) | Avelumab | Concurrently w/cisplatin-RT; 70 Gy in 35 fxs; IMRT |
| NCT02999087 | 3 | Randomized trial of avelumab-cetuximab-radiotherapy vs. SOCs in LA SCCHN (REACH) | Avelumab | Concurrently w/cetuximab-RT; 69.96 Gy in 2.12 Gy daily fxs; IMRT |
| NCT03700905 | 3 | Study of nivolumab alone or in combination with ipilimumab as immunotherapy vs. standard follow-up in surgical resectable HNSCC after adjuvant therapy (IMSTAR-HN) | Nivolumab Ipilimumab |
Neoadjuvant Nivolumab followed by surgery, adjuvant cisplatin-RT (66 Gy in 33 fx), and adjuvant Ipilimumab and Nivolumab |
| NCT03673735 | 3 | Maintenance immune check-point inhibitor following post-operative chemo-radiation in subjects with hpv-negative HNSCC (ADHERE) | Durvalumab | Induction Durvalumab followed by cisplatin-RT (66 Gy in 33 fx), and maintenance Durvalumab |
| NCT03258554 | 3 | Radiation therapy with durvalumab or cetuximab in treating patients with stage III-IVB head and neck cancer who cannot take cisplatin | Durvalumab | Concurrently with RT (IMRT) |
Selected clinical trials incorporating the use of one or more immune checkpoint inhibitor and radiation therapy are included below. When available, the dosing and sequencing for the trials is included. SBRT, Stereotactic Body Radiotherapy; RT, radiation therapy; fxs, fractions; Gy, gray; ICI, immune checkpoint inhibitor; CRT, chemoradiotherapy; IMRT, intensity-modulated radiation therapy; LA-SSCHN, locally advanced squamous cell carcinoma of the head and neck; BED, biologically equivalent dose.