Table 1. Ongoing clinical trials involving immunotherapy combined with radiotherapy for GI malignancies.
| Trial ID | Phase | Tumor type and histology | Immunotherapy | Radiation | Study design |
|---|---|---|---|---|---|
| Esophagogastric cancers | |||||
| NCT02735239 | I/II | Metastatic/locally advanced esophageal cancer (N=73) | Durvalumab ± tremelimumab | Unspecified EBRT | Non-randomized, open label trial evaluating the safety of Durvalumab ± tremelimumab in combination with oxaliplatin/capecitabine chemotherapy and standard RT |
| NCT02642809 | I | Metastatic esophageal cancer | Pembrolizumab | Brachytherapy (16 Gy in 2 fractions of 8 Gy per fraction, separated by 7–10 days between fractions | Open label trial evaluating tolerability of localized brachytherapy combined with pembrolizumab as measured by treatment related adverse events |
| NCT03377400 | II | Inoperable ESCC | Durvalumab and tremelimumab | Unspecified | Open label, single-arm study evaluating progression-free survival with combination of chemotherapy (5FU/CDDP) and Durvalumab + Tremelimumab with concurrent RT |
| NCT03437200 | II | Inoperable, early stage and locally advanced ESCC or EAC | Nivolumab ± ipilimumab | 50 Gy in 25 fractions | Randomized, open label study evaluating safety of nivolumab ± Ipilimumab in combination with standard RT and FOLFOX |
| NCT03792347 | I | Stage II/III ESCC | Pembrolizumab | 41.4 Gy in 23 fractions | Open label, single arm study evaluating the safety of preoperative pembrolizumab with standard carboplatin, paclitaxel, and RT |
| NCT02844075 | II | Stage II/III ESCC | Pembrolizumab | 41.4 Gy in 23 fractions | Open-label, single arm study evaluating pathologic response rate of patients receiving preoperative chemoradiotherapy with paclitaxel, carboplatin and pembrolizumab |
| NCT02520453 | II | ESCC (N=86) | Durvalumab | Unspecified | Randomized, double blind study evaluating treatment response of adjuvant Durvalumab or placebo for completely resected esophageal squamous cell carcinoma previously treated with neoadjuvant concurrent chemoradiotherapy |
| NCT02830594 | II | ESCC, EAC, GEJ, GAC (N=14) | Pembrolizumab | Unspecified EBRT | Open-label, single arm study evaluating pathologic response rate of pembrolizumab and palliative EBRT |
| NCT03087864 | II | Stage II EAC or GEJ (N=40) | Atezolizumab | 23 x1.8 Gy | Open-label, single arm study evaluating the feasibility of preoperative treatment with atezolizumab combined with preoperative carboplatin, paclitaxel and radiation |
| NCT03278626 | I/II | Locally advanced ESCC (N=12) | Nivolumab | 50.4 Gy (1.8 Gy/fraction x28 fractions) | Open-label single arm study evaluating the safety and efficacy treatment with Nivolumab in combination with paclitaxel, carboplatin, RT |
| NCT03544736 | I/II | ESCC or EAC or GEJ (N=30) | Nivolumab | 20-50 Gy in 25 fractions vs. 50.4 Gy in 28 fractions vs. 41.4 Gy in 23 fractions | Open-label, multi-arm, non-randomized study evaluating the safety and feasibility of treatment of advanced/inoperable vs. operable EC with Nivolumab in combination with paclitaxel, carboplatin, RT |
| NCT03257163 | II | Stage II/III dMMR or EBV+ GAC (N=40) | Pembrolizumab | Conventional Fractionation | Open-label, single arm study evaluating RFS with treatment with pembrolizumab in combination with capecitabine and RT |
| NCT03064490 | II | Stage II/III GAC or EAC (N=38) | Pembrolizumab | 41.4 Gy in 23 fractions | Open-label, non-randomized, single arm study evaluating pathologic complete response of neoadjuvant pembrolizumab in combination with carboplatin and paclitaxel and RT |
| NCT02730546 | I/II | Stage II/III GC or GEJC (N=31) | Pembrolizumab | 41.4 Gy in 23 fractions | Open-label, single arm study evaluating the safety and efficacy of pembrolizumab in combination with concurrent chemoradiotherapy, carboplatin, and paclitaxel |
| NCT03044613 | I | Stage II/III EAC, OSCC or GEJC (N=32) | Nivolumab or Relatlimab | 41.4 Gy in 23 fractions | Open-label, non-randomized study evaluating treatment with nivolumab or Relatlimab in combination with carboplatin and paclitaxel in the pre-operative setting |
| NCT03776487 | I/II | Stage II/III GC or GEJC (N=30) | Nivolumab and ipilimumab | 50 Gy in 25 fractions | Open label study evaluating the safety and toxicity profile of nivolumab in combination with ipilimumab after standard chemotherapy and followed by nivolumab in combination with fluoropyrimidine and RT |
| NCT02962063 | II | Stage II/III GEJC and GC (N=78) | Durvalumab and tremelimumab | 50 Gy in 28 fractions | Open label study evaluating the safety of treatment with durvalumab and tremelimumab in combination with carboplatin, paclitaxel and RT |
| NCT04159974 | II | Stage II/III EAC or GEJC (n=56) | Durvalumab and tremelimumab | 41.4 Gy in 23 fractions | Open label, randomized study evaluating the safety and efficacy of adding Durvalumab to standard neoadjuvant radichemotherapy and of Durvalumab +/- Tremelimumab |
| NCT02639065 | II | Stage II/III EAC or GEJC with residual disease (N=39) | Durvalumab | 41.4 Gy in 23 fractions | Open label, single arm study evaluating the safety and efficacy of durvalumab following multi-modality therapy |
| NCT03490292 | I/II | Stage II/III ESCC or EAC (N=22) | Avelumab | 41.4 Gy in 23 fractions | Open label, Non-randomized study evaluating the safety tolerability and efficacy of avelumab in combination with carboplatin, paclitaxel, and RT |
| NCT03604991 | II/III | Stage II-IV EAC, GEJC (N=514) | Ipilimumab and nivolumab | Unspecified | Open label, randomized trial evaluating the peri-operative use of Nivolumab and Ipilimumab in addition to standard of care chemotherapy and RT |
| Colorectal and anal cancers | |||||
| NCT03104439 | II | MSI-high colorectal and pancreatic cancer (N=80) | Nivolumab and ipilimumab | 24 Gy in 3 fractions | Open label study evaluating the safety and efficacy of Nivolumab and ipilimumab in combination with RT |
| NCT04663763 | II | Locally advanced rectal cancer (N=40) | Sintilimab | 25 Gy over 5 fractions | Open label, single arm study evaluating Sintilimab in combination with Capecitabine, Oxaliplatin, and RT |
| NCT04518280 | II | Locally advanced rectal cancer (N=130) | Toripalimab (Anti-PD-1) | 25 Gy over 5 fractions | Open label, randomized trial evaluating combination of Toripalimab and neoadjuvant short-course RT |
| NCT04558684 | I/II | Non-metastatic rectal cancer (N=30) | Camrelizumab | 25 Gy over 5 fractions | Open label trial evaluating preoperative treatment with camrelizumab, neoadjuvant chemotherapy, and RT |
| NCT04621370 | II | Locally advanced rectal adenocarcinoma (N=48) | Durvalumab | 25 Gy over 5 fractions or 50 Gy over 25 fractions |
Open label, randomized trial evaluating Durvalumab in combination with FOLFOX and RT |
| NCT04109755 | II | Untreated, localized rectal adenocarcinoma (N=25) | Pembrolizumab | 25 Gy over 5 fractions | Open label study evaluating the safety and efficacy of neoadjuvant Pembrolizumab and RT |
| NCT03503630 | II | Locally-advanced rectal adenocarcinoma (N=44) | COMPOUND 2055269 (Anti-PD-L1) | 25 Gy in 5 fractions | Open Label study evaluating the pCR rate following short course RT then mFOLFOX-6 in combination with COMPOUND 2055269 |
| NCT04503694 | II | Stage II-III rectal adenocarcinoma (N=60) | Nivolumab | 25 Gy in 5 fractions | Multicenter, single-arm, open label trial evaluating the efficacy of Nivolumab in combination with Regorafenib when administered before and after standard, pre-operative short course RT |
| NCT04636008 | I/II | MSI-H/dMMR non-metastatic rectal cancer (N=20) | Sintilimab (anti PD-1) | 25 Gy in 5 fractions | Open label, single arm study evaluating the safety and efficacy of Sintilimab combined with hypofractionated RT |
| NCT04411537 | II | MSS locally advanced rectal adenocarcinoma (N=50) | PD-1 antibody (unspecified) | 50 Gy in 25 fractions | Open label, single arm study evaluating pathologic complete response rate for treatment of Anti-PD1 therapy in combination with neoadjuvant capecitabine, irinotecan, and RT |
| NCT04411524 | II | MSI-H locally advanced rectal adenocarcinoma (N=50) | PD-1 antibody (unspecified) | 50 Gy in 25 fractions | Open label, single arm study evaluating pathologic complete response rate for treatment of Anti-PD1 therapy in combination with neoadjuvant capecitabine, irinotecan, and RT |
| NCT03854799 | II | Locally advanced, resectable rectal adenocarcinoma (N=101) | Avelumab | 50.4 Gy in 28 fractions | Open label, single arm study evaluating pCR of preoperative Avelumab in combination with Capecitabine and RT |
| NCT04357587 | I | MSI-H/dMMR stage II-III rectal adenocarcinoma, or oligometastatic locally advanced stage IV that are candidates for curative surgery (N=10) | Pembrolizumab | Daily fractions of 200 cGy, 5 days a week for 5 weeks |
Open label, single arm study evaluating the safety, tolerability, and feasibility of Pembrolizumab in combination with Capecitabine and RT |
| NCT03921684 | II | Locally advanced rectal adenocarcinoma (N=29) | Nivolumab | 50.4 Gy in 28 fractions | Open label, single arm study evaluating safety and pCR of Nivolumab in combination with neoadjuvant mFOLFOX6, Capecitabine, and RT |
| NCT02921256 | II | Locally advanced rectal adenocarcinoma (N=362) | Pembrolizumab | Unspecified | Open label, randomized trial evaluating the efficacy of Veliparib or pembrolizumab in combination with mFOLFOX6, capecitabine, and RT |
| NCT03127007 | I/II | Untreated, locally advanced rectal adenocarcinoma (N=54) | Atezolizumab | 45–50 Gy in 25 fractions | Open Label, Randomized trial evaluating the safety and efficacy of preoperative Atezolizumab in combination with 5-FU and RT |
| NCT04443543 | II | Locally advanced rectal adenocarcinoma (N=222) | Tislelizumab | 50 Gy in 25 fractions | Multicenter, open label, non-randomized trial evaluating CCR rate in patients treated with long course chemoradiation based on their MSI-H/dMMR status. After completion of consolidation chemotherapy, patients who reach CCR will receive organ preservation (watch and wait) strategy in place of radical surgery |
| NCT04017455 | II | Locally advanced rectal adenocarcinoma (N=38) | Atezolizumab and bevacizumab | unspecified | Open label, single arm trial evaluating the efficacy of neoadjuvant RT followed by Atezolizumab and Bevacizumab |
| NCT04124601 | II | Locally advanced rectal adenocarcinoma (N=80) | Nivolumab and ipilimumab | 50 Gy in 2 Gy fractions | Open label, randomized trial to evaluate the safety and tolerability of sequential Nivolumab and Ipilimumab in combination with chemoradiotherapy |
| NCT04293419 | II | Untreated locally advanced rectal adenocarcinoma (N=58) | Durvalumab | 50.4 Gy in 28 fractions | Open label, non-randomized, single arm study evaluating the pCR rate of Durvalumab in combination with mFOLFOX6, capecitabine, and RT |
| NCT03102047 | II | MSS stage II-IV rectal adenocarcinoma (N=45) | Durvalumab | Unspecified | Open label, single arm study evaluating the efficacy of Durvalumab after chemo-radiotherapy |
| NCT02948348 | I/II | Locally advanced, resectable rectal adenocarcinoma (N=90) | Nivolumab or ipilimumab | 45 Gy in 25 fractions | Open-label, single-arm, multicenter study evaluating the safety and efficacy of Nivolumab or ipilimumab as sequential therapy following capecitabine and RT and subsequent surgical therapy |
| NCT03299660 | II | Locally advanced, resectable rectal adenocarcinoma (N= 37) | Avelumab | 50.4 Gy in 28 fractions | Open label, single-arm study evaluating the pathological response rate of Avelumab following neoadjuvant long course RT with Capecitabine, 5-FU. This will be followed by surgical resection |
| NCT04083365 | II | Locally advanced rectal adenocarcinoma (N=60) | Durvalumab | 5040 cGy radiotherapy for 5 days per week for 5 weeks | Open-label, single arm study evaluating pCR of Durvalumab in combination with Capecitabine and RT |
| NCT03300544 | I | Rectal adenocarcinoma of any stage, excluding patients with CNS metastasis (N=3) | Talimogene laherparepvec (oncolytic herpes virus) | 50.4 Gy in 28 fractions | Open label, single-arm study evaluating the safety and feasibility of talimogene laherparepvec in combination with standard neoadjuvant chemotherapy and RT |
| NCT04130854 | II | Untreated, locally advanced rectal adenocarcinoma (N=58) | APX005M (Anti-CD40) | 25 Gy in 5 fractions | Open-label, Randomized study evaluating pCR of APX005M in combination with mFOLFOX and RT |
| NCT03916510 | I | Locally advanced rectal adenocarcinoma (N=30) | Enadenotucirev (Oncolytic virus) | 50 Gy in 25 fractions | Open-label, single arm study evaluating the safety and efficacy of Enadenotucirev in combination with Capecitabine and RT |
| NCT04304209 | II | Stage II or III CRC (N=195) | Sintilimab | 50 Gy in 25 fractions | Open label, randomized study evaluating the efficacy of Sintilimab in combination with standard chemoradiation therapy according to their MMR/MSI status |
| NCT03233711 | III | High risk stage II-IIIB anal squamous cell carcinoma (N=344) | Nivolumab | Must have received at least 54 Gy of radiation to the primary and 45 Gy to elective nodal region prior to start of trial | Randomized, open label study evaluating whether Nivolumab vs. observation alone improves disease-free survival in patients who have previously received combined modality therapy (including RT) |
| Hepatobiliary cancers | |||||
| NCT03203304 | I | Unresectable HCC (N=14) | Nivolumab or ipiliomumab | 40 Gy in 5 fractions | Open label, randomized study evaluating the safety and efficacy of SBRT followed by Nivolumab or Ipilimumab with Nivolumab |
| NCT03812562 | I | Resectable HCC (N=2) | Nivolumab | Yttrium-90 radioembolization | Open label, non-randomized study evaluating the safety and recurrence rate of standard of care yttrium Y glass microspheres followed by Nivolumab |
| NCT05063565 | II | Unresectable HCC (N=150) | Durvalumab, tremelimumab | ThereaSphere Y-90 glass microsphere therapy | Multi-center, open label, randomized study evaluating the efficacy of TheraSphere Y-90 microsphere therapy in combination with Durvalumab and Tremelimumab |
| NCT03817736 | II | Unresectable HCC (N=33) | Immune checkpoint inhibitor (unspecified) | SBRT (unspecified) | Open label, single arm study evaluating the efficacy and safety of sequential administration of TACE and SBRT with an immune checkpoint inhibitor |
| NCT04988945 | II | Unresectable HCC (N=33) | Durvalumab, tremelimumab | SBRT (unspecified) | Open label, single arm study evaluating efficacy of downstaging HCC for hepatectomy with sequential TACE, SBRT and Durvalumab + Tremelimumab |
| NCT04167293 | II/III | HCC with portal vein invasion after TACE or hepatic arterial infusion chemotherapy (n=116) | Sintilimab | 30–54 Gy in 3–6 fractions | Open label, randomized study evaluating the efficacy of SBRT followed by Sintilimab |
| NCT03753659 | II | HCC (N=30) | Pembrolizumab | RFA/MWA/Brachytheraopy | Multicenter, single arm, open-label study evaluating the clinical activity of pembrolizumab in combination with RFA/MWA/brachytherapy |
| NCT05286320 | I/II | Unresectable HCC (N=27) | Pembrolizumab | SBRT (Unspecified) | Open label, single arm study evaluating the safety and efficacy of Pembrolizumab+ lenvatinib with SBRT combinations |
| NCT03898895 | II | Unresectable biliary tract cancer (N=36) | Camrelizumab | 45 Gy total | Open label, single-arm study evaluating the efficacy and safety of Camrelizumab combined with RT |
| Pancreatic cancer | |||||
| NCT02305186 | I/II | Borderline resectable PDAC (N=68) | Pembrolizumab | 50.4 Gy in 28 Fractions | Open label, randomized study evaluating the safety and efficacy of Pembrolizumab in combination with neoadjuvant chemoradiation |
| NCT03161379 | II | Borderline resectable PDAC (N=30) | Nivolumab, GVAX pancreas vaccine | 6.6 Gy in 5 fractions | Open label, randomized study evaluating the safety and clinical activity of FOLFIRINOX along with a whole cell vaccine with immune modulating doses of cyclophsophamide and nivolumab combined with SBRT |
| NCT01595321 | N/A | Surgically resected PDAC (N=19) | GVAX | 6.6 Gy in 5 fractions | Open label, non-randomized study evaluating the safety of pancreatic tumor cell vaccine (GVAX) with immune modulating doses of cycophosphamide followed by SBRT and FOLFIRINOX after surgery |
| NCT03104439 | II | MSS and MSI high CRC and pancreatic cancer (N=80) | Nivolumab, ipilimumab | Unspecified | Open label, single arm study evaluating efficacy of combination Nivolumab, Ipilimumab, and RT |
| NCT02648282 | II | Locally advanced PDAC (N=58) | GVAX, pembrolizumab | 6.6 Gy in 5 fractions | Open label, single arm study evaluating distant metastasis free survival of GVAX combined with cyclophosphamide, pembrolizumab and RT |
| NCT03563248 | II | Localized pancreatic cancer (N=168) | Nivolumab | Unspecified | Open label, randomized study evaluating the safety and efficacy of Losartand and nivolumab in combination with FOLFIRINOX and SBRT |
| NCT02311361 | I/II | Unresectable PDAC (N=65) | Tremelimumab and/or durvalumab | 8 Gy in 1 fraction or 5 Gy in 5 fractions | Open label, multi-arm, non-randomized study evaluating the safety and efficacy of Durvalumab and/or tremelimumab with SBRT |
| NCT03104439 | II | MSI-High colorectal and pancreatic cancer (N=80) | Nivolumab and ipilimumab | 24 Gy in 3 fractions | Open label study evaluating the safety and efficacy of Nivolumab and ipilimumab in combination with RT |
GI, gastrointestinal; EBRT, external beam radiation therapy; ESCC, esophageal squamous cell carcinoma; GAC, gastric cancer; dMMR, DNA mismatch repair deficiency; EBV, Epstein-Barr Virus; EAC, Esophageal adenocarcinoma; GEJC, gastroesophageal junction adenocarcinoma; FOLFOX, oxaliplatin, leucovorin, fluorouracil; RT, radiation therapy; RFS, recurrence free survival; OSCC, oral squamous cell carcinoma; PDAC, pancreatic ductal adenocarcinoma; CRC, colorectal cancer; HCC, hepatocellular carcinoma; SBRT, stereotactic body radiation therapy; MSS, microsatellite stable; MSI, microsatellite instability; CNS, central nervous system; RT, radiation therapy; pCR, pathologic complete response; TACE, trans-arterial chemoembolization; RFA, radiofrequency ablation; MWA, microwave ablation.