Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Figures & data

Figure 1. Current clinical trials testing immunogenic cell death (ICD)-inducing chemotherapies in oncological indications. A. Distribution by immunological biomarker (biomarkers directly relevant for ICD are in bold). B. Distribution by main chemotherapeutic agent. C. Distribution by oncological indication. D. Number of clinical trials currently testing ICD-inducing chemotherapeutic regimens in combination with immunotherapy. CIK, cytokine-induced killer; CSF1, colony stimulating factor 1; DC, dendritic cell; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; NK, natural killer; TAA, tumor-associated antigen; TLR, Toll-like receptor; T_REG, regulatory T.

Table 1. Current clinical trials evaluating the therapeutic and immunological profile of ICD-inducing chemotherapeutic regimens.^*

Drug	Indication(s)	Phase	Status	Notes	Ref.
Bleomycin	Rectal cancer	II	Recruiting	As single agent in the context of electro-chemotherapy	NCT03040180
Bortezomib	Lung cancer	I	Not yet recruiting	Combined with a DRibble vaccine and DC/CIK therapy	NCT03057340
Doxorubicin	Breast carcinoma	I/II	Recruiting	Combined with epirubicin, cyclophosphamide, fluorouracil or methotrexate	NCT02897700
		II	Recruiting	Combined with decitabine, cyclophosphamide and paclitaxel, carboplatin and/or pembrolizumab	NCT02957968
			Recruiting	Combined with eribulin and cyclophosphamide	NCT02623972
			Recruiting	Combined with cyclophosphamide, ruxolitinib and paclitaxel	NCT02876302
	Pediatric solid tumors	I	Recruiting	As lyso-thermosensitive liposomal doxorubicin	NCT02536183
Epirubicin	Breast carcinoma	I/II	Recruiting	Combined with doxorubicin, cyclophosphamide, fluorouracil or methotrexate	NCT02897700
		II	Recruiting	Combined with paclitaxel, cyclophosphamide and MEDI4736	NCT02685059
				Combined with docetaxel, cyclophosphamide/ capecitabine or fluorouracil/cyclophosphamide	NCT02897050
				Combined with docetaxel, cyclophosphamide, fluorouracil, trastuzumab or pertuzumab	NCT03144947
				Combined with cyclophosphamide and fluorouracil	NCT02742051
				Combined with docetaxel, cyclophosphamide, paclitaxel, tocotrienol, trastuzumab or pertuzumab	NCT02909751
Idarubicin + mitoxantrone	Acute promyelocytic leukemia	III	Recruiting	Combined with arsenic trioxide, tretinoin, cytarabine, mercaptopurine and methotrexate	NCT02688140
Oxaliplatin	Colorectal carcinoma	n.s.	Recruiting	Combined with 5-fluorouracil and bevacizumab	NCT02817178
		I	Recruiting	Combined with trifluridine, bevacizumab and nivolumab	NCT02848443
		II	Suspended	Combined with 5-fluorouracil, leucovorin, bevacizumab, capecitabine, Ad-CEA vaccine and avelumab	NCT03050814
	Gastrointestinal cancer	IV	Not recruiting	Combined with cinobufotalin	NCT02860429
	Gastric cancer	II	Recruiting	Combined with capecitabine, epirubicin and pembrolizumab	NCT02918162
	Pancreatic cancer	I	Recruiting	Combined with folinic acid, irinotecan, 5-fluorouracil, paclitaxel, gemcitabine and a DC-based vaccine	NCT02548169

Abbreviations: Ad-CEA, adenovirus vector encoding carcinoembryonic antigen; CIK, cytokine-inducer killer; DC, dendritic cell; n.s., not specified

* Initiated between 1^st April 2015 and 30^th June 2017.

Table 2. Current clinical trials evaluating the therapeutic and immunological profile of cyclophosphamide-based chemotherapy.^*

Indication(s)	Phase	Status	Notes	Ref.
Acute lymphoblastic leukemia	II	Recruiting	Combined with standard-of-care chemotherapy	NCT02828358
Acute myeloid leukemia	III	Completed	Combined with standard-of-care chemotherapy and anti-lymphocyte globulin	NCT02461121
B-cell lymphoma	I/II	Recruiting	Combined with fludarabine and CD19-specific CAR-T cells	NCT03146533
Breast carcinoma	I	Unknown	Combined with radiotherapy	NCT02441270
		Recruiting	Combined with indomethacin, omeprazole, dietary supplements (e.g., multivitamins) and IRX-2	NCT02950259
	II	Recruiting	Combined with doxorubicin, paclitaxel, carboplatin and pembrolizumab	NCT02957968
			Combined with docetaxel, capecitabine, fluorouracil and epirubicin	NCT02897050
			Combined with everolimus, letrozole, fluorouracil and epirubicin	NCT02742051
		Not recruiting	Combined with peptide vaccination	NCT03012100
Chronic lymphocytic leukemia	II	Not recruiting	Combined with rituximab, fludarabine, bendamustine, lenalidomide and ACT	NCT02530515
DLBCL	I	Recruiting	Combined with fludarabine and CD19-specific CAR-T cells	NCT02431988
EBV-associated malignancies^**	I/II	Recruiting	Combined with fludarabine and PDCD1-deficient EBV-specific CTLs	NCT03044743
Esophageal cancer	II	Recruiting	Combined with PDCD1-deficient CTLs and IL2	NCT03081715
Gastrointestinal cancer	I	Not recruiting	Combined with ACT, IL2 and pembrolizumab	NCT02757391
Gynecological tumors	I	Recruiting	Combined with epacadostat and DPX-Survivac	NCT02785250
	II	Recruiting	Combined with pembrolizumab and bevacizumab	NCT02853318
	II	Not recruiting	Combined with PD0360324	NCT02948101
Hematological malignancies	I/II	Not recruiting	Combined with a DC-based vaccine and GM-CSF	NCT02709993
	III	Recruiting	Combined with tacrolimus and methotrexate	NCT02345850
Hepatocellular carcinoma	I/II	Not recruiting	Combined with IMA970 A plus CV8102	NCT03203005
Lung cancer	I	Withdrawn	Combined with DC-based vaccine	NCT02419170
		Not recruiting	Combined with radiotherapy	NCT02579005
		Recruiting	Combined with PDCD1-deficient CTLs and IL2	NCT02793856
Lung cancer and mesothelioma	I/II	Recruiting	Combined with ACT and IL2	NCT02408016
Melanoma	I/II	Recruiting	Combined with polyICLC and MHP vaccine	NCT02425306
	I	Recruiting	Combined with pembrolizumab and ONCOS-102	NCT03003676
Mesothelioma	I/II	Recruiting	Combined with premetrexed/cisplatin and ONCOS-102	NCT02879669
Multiple myeloma	I	Completed	Combined with lenalidomide and elotuzumab	NCT02655458
Neuroendocrine tumors	II	Recruiting	Combined with IFNα	NCT02838342
Osteosarcoma	I	Recruiting	Combined with sirolimus, methotrexate and zoledronic acid	NCT02517918
Prostate cancer	I	Recruiting	Combined with DNA-based vaccine	NCT02390063
			Combined with cytoxan and testosterone	NCT02995330
		Not recruiting	Combined with PDCD1-deficient CTLs and IL2	NCT02867345
Renal cell carcinoma	I	Not recruiting	Combined with PDCD1-deficient CTLs and IL2	NCT02867332
Sarcoma	II	Recruiting	Combined with pembrolizumab	NCT02406781
Solid tumors	I	Not recruiting	Combined with a TLR8 agonist and pegfilgrastim	NCT02650635
	I/II	Not recruiting	Combined with a DC-based vaccine and GM-CSF	NCT02705703
		Recruiting	Combined with fludarabine, neoantigen-specific T cells, PDCD1 inhibition and IL2	NCT03171220

Abbreviations: ACT, adoptive cell transfer; CAR, chimeric antigen receptor; CTL, cytotoxic T lymphocyte; DC, dendritic cell; DLBCL, diffuse large B-cell lymphoma; DPX, DepoVax™; EBV, Epstein-Barr virus; GM-CSF, granulocyte macrophage colony stimulating factor; IFN, interferon; IL, interleukin; MHP, melanoma helper peptides; polyICLC, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose; TAA, tumor-associated antigen; TLR, Toll-like receptor

* Initiated between 1^st April 2015 and 30^th June 2017

** Including gastric carcinoma, nasopharyngeal carcinoma, T-cell lymphoma, Hodgkin lymphoma and DLBCL.