Table 2.
Clinical trials involving intratumoral immunotherapies started between January 2018 and June 2021
| Single type of i.t. immunotherapy | |||||||
|---|---|---|---|---|---|---|---|
| Single type of i.t. immunotherapy | Subtype of i.t. immunotherapy | Agent for i.t. immunotherapy | Non-i.t. co-therapy[i.t. co-therapy] | Indications | Trial status | Phases | NCT Number |
| Adoptive transfer of lymphocytes | NK cells | NK cells | - | Glioma | Not yet recruiting | I | NCT04254419 |
| CYNK001 | - | Astrocytoma, Glioblastoma | Active, not recruiting | I | NCT04489420 | ||
| CAR-T cells | HER2(EQ)BBzeta/CD19t+ T cells | - | Glioma | Recruiting | I | NCT03389230 | |
| Nectin4/FAP-targeted CAR-T cells (expressing IL7 and CCL19, or IL12) | - | Nectin4-positive solid tumors | Recruiting | I | NCT03932565 | ||
| Cytokine | GM-CSF | N/D | Pembrolizumab, Cryoimmunotherapy, Imiquimod | Breast cancer | Terminated | I | NCT03982004 |
| GM-CSF + IFNα2b + IL12 single chain + IL15sushi (saline-formulated mixture of 4 mRNAs) | SAR441000 (BNT131) | Cemiplimab | Solid tumors | Recruiting | I | NCT03871348 | |
| IL2 | Aldesleukin | - | Melanoma | Recruiting | III | NCT03233828 | |
| IL12 (plasmid) | Tavokinogene telseplasmid + electroporation (Tavo-EP) | Nivolumab | Melanoma | Recruiting | II | NCT04526730 | |
| Pembrolizumab, Epacadostat | HNSCC | Recruiting | II | NCT03823131 | |||
| Pembrolizumab, Nab-paclitaxel | TNBC | Recruiting | II | NCT03567720 | |||
| IL12 (mRNA encapsulated in lipid nanoparticles) | MEDI1191 | Durvalumab | Solid tumors | Recruiting | I | NCT03946800 | |
| ICD-inducing synthetic agent (confirmed or candidate) | Chemotherapy | Cisplatin | - | NSCLC | Recruiting | I | NCT04809103 |
| INT230-6 | Surgery | Breast cancer | Recruiting | II | NCT04781725 | ||
| All or subsets of the following drugs: Cisplatin, Carboplatin, Cyclophosphamide, Doxorubicin, Gemcitabine, Paclitaxel, Pemetrexed, Vinorelbine | [All or subsets of the following drugs: Etoposide, Ifosfamide, Niraparib, Olaparib, Rucaparib, Topotecan], Surgery | Fallopian tube cancer, Ovarian cancer, Peritoneal cancer | Recruiting | I | NCT04701645 | ||
| Oncolytic peptide | CyPep-1 | - | Advanced solid tumors | Recruiting | I/II | NCT04260529 | |
| LTX-315 | Pembrolizumab | Advanced solid tumors | Not yet recruiting | II | NCT04796194 | ||
| mAb – Immune checkpoint antagonist | Anti-CD39 | SRF617 | Gemcitabine, Nab-paclitaxel, Pembrolizumab | Solid tumors | Recruiting | I | NCT04336098 |
| Anti-PD1 | Cemiplimab | Surgery | CSCC | Completed | I | NCT03889912 | |
| Nivolumab | - | Kaposi sarcoma | Active, not recruiting | I | NCT03316274 | ||
| Anti-PD1 ± Anti-CTLA4 | Ipilimumab, Nivolumab | Cyclophosphamide, Cryosurgery | Prostate cancer | Recruiting | II | NCT04090775 | |
| Ipilimumab, Pembrolizumab | - | Breast cancer, Cervical cancer, CRC, HNSCC, Liver cancer, Lung cancer, Melanoma, Ovarian cancer, Pancreatic cancer, Renal cancer | Recruiting | II/III | NCT03755739 | ||
| mAb – Immune checkpoint agonist | Anti-CD40 | 2141 V-11 | - | Melanoma, Other solid tumors | Recruiting | I | NCT04059588 |
| ABBV-927 | - | HNSCC | Terminated | I | NCT03818542 | ||
| rAd.CD40L | Pembrolizumab | Melanoma | Withdrawn | I/II | NCT02719015 | ||
| Selicrelumab | Atezolizumab | B-cell non-Hodgkin lymphoma | Terminated | I | NCT03892525 | ||
| nti-CD137 | Urelumab | Nivolumab | Solid tumors | Not yet recruiting | I/II | NCT03792724 | |
| mAb – Conjugated | Anti-EDB-FN fused to IL2 or TNFα | L19IL2 + L19TNF | - | Non-melanoma skin cancers | Recruiting | II | NCT04362722 |
| Anti-GD2 fused to IL2 | IT-hu14.18-IL2 (EMD 273063) | Radiotherapy, Ipilimumab, Nivolumab | Melanoma | Recruiting | I/II | NCT03958383 | |
| Anti-mesothelin conjugated with Pseudomonas exotoxin | LMB-100 | Ipilimumab | Mesothelioma | Recruiting | I | NCT04840615 | |
| SIRPα-Fc-CD40L | SL-172154 | - | CSCC, HNSCC | Recruiting | I | NCT04502888 | |
| mAb – Mixed | Anti-CD20/Anti-CD38/Anti-PD1/Anti-HER2 | Daratumumab, Nivolumab, Obinutuzumab, Pembrolizumab, Rituximab, Trastuzumab | [Belinostat, Carfilzomib, Gemcitabine, Romidepsin] | Breast cancer, Lymphoma | Suspended | I | NCT03432741 |
| Anti-CD40 + anti-EGFR conjugated with Pseudomonas exotoxin | 2141-V11, D2C7 | - | Glioma | Recruiting | I | NCT04547777 | |
| (Anti-ILT3/Ani-ILT4) + Anti-PD1 | MK-0482, MK-4830, Pembrolizumab | Surgery | Solid tumors | Not yet recruiting | I | NCT04541108* (Exp. arm 3) | |
| Nonpathogenic bacterium | Attenuated Clostridium | C. novyi-NT | Pembrolizumab, Doxycycline | Breast cancer, Endocrine cancer, Gastrointestinal cancer, Genital cancer, Lung cancer, Nervous system cancer, Sarcoma, Urothelial cancer | Recruiting | I | NCT03435952 |
| Oncolytic viruses | Adenovirus | AdAPT-001 | - | Solid tumors | Recruiting | I | NCT04673942 |
| CAdVEC | HER2-specific CAR T cell | HER-2-positive solid tumors | Recruiting | I | NCT03740256 | ||
| DNX-2440 | Surgery | Breast cancer, CRC, Kidney cancer, Liver cancer, Gastrointestinal cancer, Melanoma, Periampullary cancer, Sarcoma, SCC | Recruiting | I | NCT04714983 | ||
| LOAd703 | Chemotherapy (standard-of-care, gemcitabine) | Biliary cancer, CRC, Ovarian cancer, Pancreatic cancer | Recruiting | I/II | NCT03225989 | ||
| ONCOS-102 | Cyclophosphamide, DCVac/Pca | Prostate cancer | Terminated | I/II | NCT03514836 | ||
| ORCA-010 | - | Prostate cancer | Recruiting | I/II | NCT04097002 | ||
| Telomelysin (OBP-301) | Carboplatin, Paclitaxel, Radiotherapy | Gastroesophageal cancer | Recruiting | I | NCT04391049 | ||
| Pembrolizumab, Radiotherapy | HNSCC | Recruiting | II | NCT04685499 | |||
| Herpesvirus | HSV G207 | Radiotherapy | Glioma | Not yet recruiting | II | NCT04482933 | |
| OH2 | Cisplatin, Fluorouracil, LP002 | Digestive system cancer | Recruiting | I | NCT04755543 | ||
| ONCR-177 | Pembrolizumab | Solid tumors | Recruiting | I | NCT04348916 | ||
| OrienX010 | Toripalimab | Melanoma | Active, not recruiting | I | NCT04197882 | ||
| JS001 | Melanoma | Recruiting | I | NCT04206358 | |||
| RP1 | Cemiplimab | SCC | Recruiting | II | NCT04050436 | ||
| - | SCC | Recruiting | I | NCT04349436 | |||
| RP3 | Undefined anti-PD1 | Visceral tumors | Recruiting | I | NCT04735978 | ||
| T-VEC | Atezolizumab | CRC, TNBC | Active, not recruiting | I | NCT03256344 | ||
| - | Non-melanoma skin cancer | Recruiting | I | NCT03458117 | |||
| Atezolizumab | Breast cancer | Recruiting | I | NCT03802604 | |||
| Pembrolizumab, Surgery | Melanoma | Recruiting | II | NCT03842943 | |||
| - | Angiosarcoma of skin | Active, not recruiting | II | NCT03921073 | |||
| - | Kaposi sarcoma | Not yet recruiting | II | NCT04065152 | |||
| Pembrolizumab | Melanoma | Active, not recruiting | II | NCT04068181 | |||
| Nivolumab, Surgery | Melanoma | Recruiting | II | NCT04330430 | |||
| Surgery | Melanoma | Recruiting | II | NCT04427306 | |||
| Radiotherapy | Sarcoma | Recruiting | I/II | NCT04599062 | |||
| VG161 | - | Solid tumors | Recruiting | I | NCT04758897 | ||
| - | Liver cancer | Recruiting | I | NCT04806464 | |||
| Paramyxovirus | MV-s-NAP | - | Breast cancer | Recruiting | I | NCT04521764 | |
| TMV-018 | 5-fluorocytosine, Undefined anti-PD1 | Gastrointestinal cancer | Withdrawn | I | NCT04195373 | ||
| Picornavirus | V937 (Coxsackievirus A21) | Pembrolizumab | Melanoma | Recruiting | II | NCT04152863 | |
| Pembrolizumab | Gastric cancer, Liver cancer, SCC, TNBC, Other solid tumors | Recruiting | I/II | NCT04521621 | |||
| PVSRIPO | Surgery | Breast cancer | Recruiting | I | NCT03564782 | ||
| - | Melanoma | Active, not recruiting | I | NCT03712358 | |||
| Pembrolizumab | Brain tumors | Recruiting | II | NCT04479241 | |||
| Nivolumab | Melanoma | Withdrawn | I | NCT04125719 | |||
| Poxvirus | ASP9801 | - | (Sub)cutaneous tumors, Visceral tumors | Recruiting | I | NCT03954067 | |
| BT-001 | Pembrolizumab | Melanoma, Merkell cell carcinoma, NSCLC, Sarcoma, TNBC | Recruiting | I/II | NCT04725331 | ||
| OVV-01 | Atezolizumab, Pembrolizumab | Solid tumors | Active, not recruiting | I | NCT04787003 | ||
| Pexa-Vec (JX-594) | Cemiplimab | Kidney cancer | Recruiting | I/II | NCT03294083 | ||
| ZKAB001 | Melanoma | Not yet recruiting | I/II | NCT04849260 | |||
| TBio-6517 | Pembrolizumab | CRC, TNBC, Other solid tumors | Recruiting | I/II | NCT04301011 | ||
| Rhabdovirus | VSV-IFNbetaTYRP1 | VSV-IFNbetaTYRP1 | Melanoma | Recruiting | I | NCT03865212 | |
| Voyager V1 | Cemiplimab, Voyager V1 | Melanoma | Recruiting | II | NCT04291105 | ||
| MG1-E6E7 | Ad-E6E7, Atezolizumab, MG1-E6E7 | HPV-associated cancers | Active, not recruiting | I | NCT03618953 | ||
| MG1-MAGEA3 | Ad-MAGEA3, Cyclophosphamide, MG1-MAGEA3, Pembrolizumab | Melanoma, SCC | Withdrawn | I | NCT03773744 | ||
| Poxvirus | ASP9801 | - | (Sub)cutaneous tumors, Visceral tumors | Recruiting | I | NCT03954067 | |
| BT-001 | Pembrolizumab | Melanoma, Merkell cell carcinoma, NSCLC, Sarcoma, TNBC | Recruiting | I/II | NCT04725331 | ||
| OVV-01 | Atezolizumab, Pembrolizumab | Solid tumors | Active, not recruiting | I | NCT04787003 | ||
| Pexa-Vec (JX-594) | Cemiplimab | Kidney cancer | Recruiting | I/II | NCT03294083 | ||
| ZKAB001 | Melanoma | Not yet recruiting | I/II | NCT04849260 | |||
| TBio-6517 | Pembrolizumab | CRC, TNBC, Other solid tumors | Recruiting | I/II | NCT04301011 | ||
| Other virus-basedimmunotherapies | Adenovirus | Ad-P53 | Nivolumab | Solid tumors | Terminated | I/II | NCT02842125 |
| Atezolizumab, Durvalumab, Nivolumab, Pembrolizumab | Lymphoma, Solid tumors | Recruiting | II | NCT03544723 | |||
| Ad-RTS-hIL12 | Veledimex, Surgery | Glioblastoma | Active, not recruiting | I | NCT03679754 | ||
| Veledimex, Nivolumab, Surgery | Glioblastoma | Active, not recruiting | I | NCT03636477 | |||
| Veledimex, Cemiplimab, Surgery | Glioblastoma | Active, not recruiting | II | NCT04006119 | |||
| MTG201 | Nivolumab | Mesothelioma | Recruiting | II | NCT04013334 | ||
| Arenavirus | HB-201 | HB-201, HB-202 | HPV16-positive HNSCC | Recruiting | I/II | NCT04180215 | |
| Chemoradiation | HPV16-positive oropharynx cancer, HPV16-positive cervical cancer | Recruiting | I | NCT04630353 | |||
| Flavivirus | PV-001-DV | PV-001-DC | Melanoma | Not yet recruiting | I | NCT03990493 | |
| Orthomyxovirus | Unattenuated influenza vaccine | Surgery | CRC | Recruiting | II | NCT04591379 | |
| Quadrivalent inactivated influenza vaccine | Ipilimumab, Nivolmab, Pembrolizumab, Quadrivalent inactivated influenza vaccine, Surgery | Melanoma | Not yet recruiting | I | NCT04697576 | ||
| Poxvirus | MVA-BN-Brachyury | Atezolizumab, PROSTVAC, Surgery | Prostate cancer | Withdrawn | II | NCT04020094 | |
| PRR agonist | RIG-1 agonist | MK-4621 | Pembrolizumab | Solid tumors | Completed | I | NCT03739138 |
| STING agonist | ADU-S100 (MIW815) | Pembrolizumab | HNSCC | Active, not recruiting | II | NCT03937141 | |
| BI 1387446 | Ezabenlimab | Neoplasms | Recruiting | I | NCT04147234 | ||
| E7766 | - | Lymphoma, Solid tumors | Recruiting | I | NCT04144140 | ||
| IMSA101 | Undefined ICIs | Solid tumors | Recruiting | I/II | NCT04020185 | ||
| MK-1454 | Pembrolizumab | HNSCC | Active, not recruiting | II | NCT04220866 | ||
| SYNB1891 | Atezolizumab | Lymphoma, Solid tumors | Recruiting | I | NCT04167137 | ||
| TLR3 agonist | BO-112 | Nivolumab, Radiotherapy, Surgery | Sarcoma | Recruiting | I | NCT04420975 | |
| Pembrolizumab | Liver cancer | Not yet recruiting | Early I | NCT04777708 | |||
| Pembrolizumab | CRC, Gastroesophageal cancer | Recruiting | II | NCT04508140 | |||
| Pembrolizumab | Melanoma | Recruiting | II | NCT04570332 | |||
| Poly-ICLC (Hiltonol) | Surgery | Mesothelioma | Recruiting | I | NCT04525859 | ||
| TLR4 agonist | G100 | - | Lymphoma | Withdrawn | II | NCT03742804 | |
| TLR7 agonist | LHC 165 | PDR001 | Solid tumors | Active, not recruiting | I | NCT03301896 | |
| TLR7/8 agonist | NKTR-262 | Bempegaldesleukin, Nivolumab | Breast cancer, CRC, HNSCC, Skin cancers, Sarcoma | Active, not recruiting | I/II | NCT03435640 | |
| TransCon | Pembrolizumab | Solid tumors | Recruiting | I/II | NCT04799054 | ||
| TLR8 agonist | Motolimod (VTX-2337) | Nivolumab, Surgery | HNSCC | Recruiting | I | NCT03906526 | |
| TLR9 agonist | Cavrotolimod (AST-008) | Cemiplimab, Pembrolizumab | Skin cancers, Other solid tumors | Recruiting | I/II | NCT03684785 | |
| CMP-001 | Atezolizumab, Radiotherapy | NSCLC | Completed | I | NCT03438318 | ||
| Cemiplimab | Skin cancers, TNBC | Not yet recruiting | II | NCT04916002 | |||
| Ipilimumab, Nivolumab, Radiotherapy | CRC, Other solid tumors | Unknown status | I | NCT03507699 | |||
| Nivolumab, Surgery | Melanoma, Lymph node cancer | Active, not recruiting | II | NCT03618641 | |||
| Nivolumab, Surgery | Melanoma | Recruiting | II | NCT04401995 | |||
| Nivolumab | Melanoma | Recruiting | II/III | NCT04695977 | |||
| Nivolumab | Melanoma | Recruiting | II | NCT04698187 | |||
| Pembrolizumab | Lymphoma | Recruiting | I/II | NCT03983668 | |||
| Pembrolizumab | HNSCC | Recruiting | II | NCT04633278 | |||
| Pembrolizumab, Surgery | Melanoma | Recruiting | II | NCT04708418 | |||
| Radiotherapy | TNBC | Not yet recruiting | II | NCT04807192 | |||
| SD-101 | Epacadostat, Radiotherapy | Solid tumors, Lymphoma | Active, not recruiting | I/II | NCT03322384 | ||
| Nivolumab, Radiotherapy | Pancreatic cancer | Recruiting | I | NCT04050085 | |||
| Abiraterone acetate, Leuprolide acetate, Pembrolizumab, Prednisone, Radiotherapy | Prostate cancer | Recruiting | II | NCT03007732 | |||
| Tilsotolimod (IMO-2125) | ABBV-181, ABBV-368, Nab-paclitaxel | HNSCC | Recruiting | I | NCT04196283 | ||
| Ipilimumab | Metastatic Melanoma | Active, not recruiting | III | NCT03445533 | |||
| Ipilimumab, Nivolumab | Solid tumors | Recruiting | II | NCT03865082 | |||
| Undefined CpG ODN | Electroporation, FOLFIRINOX, Nivolumab | Pancreatic cancer | Recruiting | I | NCT04612530 | ||
| Semi-synthetic adjuvants | Biopolymer | Copaxone (glatiramer acetate) | Surgery | Skin cancers | Recruiting | I | NCT03982212 |
| IP-001 (N-dihydrogalactochitosan) | Thermal ablation | Solid tumors | Recruiting | I/II | NCT03993678 | ||
| Therapeutic vaccine | DC-based | Ad-CCL21-DC | Pembrolizumab | NSCLC | Recruiting | I | NCT03546361 |
| DCVax-Direct | - | Breast cancer, Lung cancer | Unknown status | I | NCT03638765 | ||
| DNA-based | IFx-Hu2.0 | - | Melanoma | Active, not recruiting | I | NCT03655756 | |
| - | Merkel cell carcinoma, SCC | Recruiting | I | NCT04160065 | |||
| Mixed types of i.t. immunotherapy | |||||||
|---|---|---|---|---|---|---|---|
| Types of i.t. immunotherapy | Subtypes of i.t. immunotherapy | Agents for i.t. immunotherapy | Non-i.t. co-therapy[i.t. co-therapy] | Indications | Trial status | Phases | NCT Number |
| Adoptive transfer of CAR-T cells + Chemotherapy + PRR agonist | CAR-T cells + ICD chemoinducers (?) + TLR9 agonist | CAR-T cells secreting scFv against OX40, Drug-eluting beads, CpG ODN | Microwave ablation | Lung cancer, Liver cancer | Recruiting | I | NCT04952272 |
| Adoptive transfer of DCs + mAb | DCs + Anti-CTLA4 + Anti-PDL1 | CD1c(BDCA-1)+ myeloid DCs, Ipilimumab, Avelumab | Nivolumab | Solid tumors | Completed | I | NCT03707808 |
| DCs + Anti-CTLA4 + Anti-PDL1 | CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid DCs, Ipilimumab, Avelumab | Pembrolizumab, Radiotherapy | NSCLC | Recruiting | II | NCT04571632 | |
| Cytokine + Immune checkpoint | IL23 + IL36γ + OX40L (encoded by 3 mRNAs encapsulated in lipid nanoparticles) | mRNA-2752 | Durvalumab | HNSCC, Non-hodgkin lymphoma, TNBC, Urothelial cancer, Other solid tumors | Recruiting | I | NCT03739931 |
| Cytokine + nonpathogenic bacterium | BCG + IL2 | OncoTICE, Aldesleukin | - | Melanoma | Not yetrecruiting | II/III | NCT03928275 |
| Immune checkpoint + PRR | CD40L + CD70 + TLR4 (encoded by 3 naked mRNAs) | TriMix | Chemotherapy, Surgery | Breast cancer | Recruiting | I | NCT03788083 |
| mAb + PRR agonist | Anti-CTLA4 + TLR4 agonist | Ipilimumab, GLA-SE | FOLFOX, Nivolumab | CRC | Withdrawn | I | NCT03982121 |
| Anti-CTLA4 + TLR9 agonist | Ipilimumab, Tilsotolimod | Nivolumab | Solid tumors | Recruiting | I | NCT04270864 | |
| Anti-PD1 + TLR8 agonist | Nivolumab, Motolimod | - | HNSCC | Recruiting | I | NCT04272333* | |
| Anti-OX40 + TLR9 agonist | INCAGN01949, CMP-001 | - | Pancreatic cancer, Other solid tumors | Not yet recruiting | I/II | NCT04387071 | |
| Anti-OX40 + TLR9 agonist | BMS-986178, SD-101 | Radiotherapy | Lymphoma | Recruiting | I | NCT03410901 | |
| Anti-OX40 + TLR9 agonist | BMS-986178, SD-101 | BMS-986178 | Solid tumors | Recruiting | I | NCT03831295 | |
| mAb + Targeted chemotherapy | SUMOylation inhibitor + (Anti-EGFR or Anti-PDL1) | TAK-981, Cetuximab, Avelumab | - | HNSCC | Recruiting | I | NCT04065555* |
| mAb + PRR agonist | (Anti-CTLA4/Anti-LAG3/NLRP3 agonist) + Anti-PD1 | Ipilimumab, Relatlimab, BMS-986299, Nivolumab | Surgery | Solid tumors | Not yet recruiting | I | NCT04541108* (Exp. arm 1&2) |
| Chemotherapy + PRR agonist | ICD chemoinducers (candidates) ± STING agonist | 5-Fluorouracil, Carboplatin, Paclitaxel, TAK-676 | |||||
Source: clinicaltrials.gov. Search queries: Condition or disease: “cancer” OR “tumor” OR “neoplasm” OR “carcinoma” OR “sarcoma” OR “melanoma” OR “lymphoma” OR “leukemia” OR “myeloma”. Other terms: “intratumoral” OR “intratumor” OR “intralesional” OR “intralesion” OR “local injection” OR “local administration”. Study starts from “01/01/2018” to “08/06/2021”. Study type: Interventional. Phase: Early Phase 1 to Phase 4. Among the studies that came out from this search, we excluded the ones that were not involving immunotherapy. 153 studies were found to finally concern intratumoral immunotherapies. The subsection “Mixed types of i.t. immunotherapy” regroups trials in which various subtypes of immunotherapies are co-injected i.t. Of note, when oncolytic viruses, adoptive immune cells, or DC-based vaccines where genetically engineered to express a transgene (e.g. cytokine), they were described in their respective category rather than considered as combination treatments. The clinical trials testing drug administration through the CIVO device are indicated by an asterisk (*). BCG, Bacillus Calmette–Guérin; CAR-T, chimeric antigen receptor T cell; CRC, colorectal cancer; CSCC, cutaneous squamous cell carcinoma; DC, dendritic cell; EDB-FN, extradomain B of fibronectin; FOLFIRINOX, folinic acid+fluorouracil+irinotecan+oxaliplatin; FOLFOX, folinic acid+fluorouracil+oxaliplatin; HNSCC, head and neck squamous cell carcinoma; ICD, immunogenic cell death; ICI, immune checkpoint inhibitor; i.t., intratumor; mAb, monoclonal antibody; Nab, nanoparticle albumin-bound; N/D, not determined; NK, natural killer; NSCLC, non-small-cell lung carcinoma; ODN, oligodeoxynucleotide; PRR, pattern recognition receptor; SCC, squamous cell carcinoma; TNBC, triple negative breast cancer.