Table 3:
Relevant prospective trials involving PD-1 Blockade and RT. NSCLC = non-small cell lung cancer, PFS= progression-free survival, AE = adverse event, SCC= squamous cell carcinoma, DFS = disease-free survival
| Trial | ClinicalTrials.gov ID | Setting | Phase/Type | Treatment | Endpoint | Toxicity | Status |
|---|---|---|---|---|---|---|---|
| Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials 41 |
NCT02492568
NCT02444741 |
Metastatic NSCLC | 1/2 | Immunotherapy with or without RT | Response rate | High grade events uncommon, no new safety signals | Published |
| Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial42 | NCT02434081 | Stage III NCSCC | 2 | Chemoradiation with concurrent nivolumab | Safety | Anemia (47.5%), fatigue (45%), pneumonitis (42.5%); 55% mild, 30.3% moderate, 10.9% severe | Published |
| Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN) | NCT03383094 | Head and neck (intermediate/high risk p16+, locoregionally advanced) | 2 | RT and concurrent cisplatin versus RT and concurrent and adjuvant pembrolizumab | PFS | Lead-in results reported for 8 patients; included one DLT (grade 4 adrenal insufficiency), one grade 3 weight loss, one grade 3 infusion reaction | Recruiting |
| Safety evaluation of nivolumab (Nivo) concomitant with cetuximab-radiotherapy for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG 3504 44 | NCT02764593 | Head and neck (Intermediate and high risk) | 1 | Chemoradiation with cetuximab with addition of concurrent nivolumab (various schedules) | DLT | 1 DLT (mucositis) out of 8 evaluable patients along with one other grade 3 AE (lipase increase) | Initial safety report presented |
| Targeting PD-1 Therapy Resistance With Focused High or High and Low Dose Radiation in SCCHN | NCT03085719 | Metastatic head and neck | 2 | High and/or low dose RT with pembrolizumab on day one | Overall response rate | Pending Report | Recruiting |
| A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): First results of the GORTEC 2015–01 “PembroRad” trial45 | NCT02707588 | Head and neck; patients unfit for high dose cisplatin with nonoperable disease | 2 | RT with cetuxumab or pembrolizumab | Locoregional control | Less grade ≥3 mucositis and dermatitis in pembrolizumab arm; similar dysphagia | Early results presented |
| A Study of Chemoradiation Plus Pembrolizumab for Locally Advanced Laryngeal Squamous Cell Carcinoma | NCT02759575 | Locally advanced head and neck (larynx) | 1/2 | RT with concurrent cisplatin and concurrent pembrolizumab | Rate of grade 3 or 4 AEs | Pending Report | Active |
| Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy (IMSTAR-HN) | NCT03700905 | Postoperative head and neck SCC | 3 | Nivolumab or nivolumab plus ipilimumab following surgical resection and adjuvant RT (with or without chemo) | DFS | Pending report | Open |
| Anti PD-1 Antibody With Radiation Therapy in Patients With HER2-negative Metastatic Breast Cancer | NCT03430479 | Metastatic Her2-negative breast | I/2 | RT + nivolumab + hormonal therapy | DLT | Pending report | Active |
| Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors | NCT02608385 | Limited metastatic solid tumors | 1 | 3 or 5 doses of SBRT to chosen metastatic sites followed by pembrolizumab | Recommended SBRT dose | Pending report | Active |
| Safety and Feasibility of PD-1 Blockade in the Treatment of Rectal Cancer | NCT04357587 | Rectal cancer | 1 | RT with concurrent capecitabine with pembrolizumab given on days 1, 22, and 43 | Rate of AEs, completion of therapy, feasibility | Pending report | Recruiting |
| A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers | NCT03115801 | Metastatic genitourinary cancers | 2 | Immunotherapy (nivolumab, atezolizumab, or pembrolizumab) with or without RT | Response rate | Pending report | Recruiting |
| Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy | NCT03543189 | Grade group 5 prostate cancer | 1–2 | ADT followed by nivolumab and RT | Safety, replase-free survival | Pending report | Recruiting |
| Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma | NCT03743662 | Recurrent MGMT Methylated Glioblastoma | 2 | Hypofractionated reirradiation with concurrent nivolumab followed by adjuvant nivolumab | Overall survival | Pending report | Recruiting |
| Pembrolizumab for Newly Diagnosed Glioblastoma (PERGOLA) | NCT03899857 | Newly diagnosed glioblastoma | 2 | RT with concurrent temozolomide with addition of concurrent Pembrolizumab | OS | Pending report | Not yet recruiting |
| A Multicenter, Phase 3, Randomized Trial of Sequencial Chemoradiotherapy With or Without Toripalimab (PD-1 Antibody) in Newly Diagnosed Early-Stage Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (ENKTL) | NCT04365036 | Early stage NK/T Cell lymphoma | 3 | Toripalimab and induction chemotherapy followed by RT with concurrent toripalimab versus induction followed by RT | PFS | Pending report | Recruiting |
| Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11) | NCT04221945 | Locally advanced cervix | 3 | Chemoradiation with or without concurrent pembrolizumab | PFS, OS | Pending report | Recruiting |