Table 3.

Industry-driven clinical trials targeting solid tumors

Industry sponsor	Target antigen CAR construct	Trial (ClinicalTrials.gov identifier)	Indication	Approach	Clinical data
Atara with MSKCC	Mesothelin scFv.1XX.ζ	NCT02414269	Malignant pleural disease from pleural mesothelioma or secondary metastatic disease (lung and breast cancers)	Intrapleural administration of a CAR co-expressing an icaspase-9 safety switch	Results presented at the AACR 2019 [103] n = 21, including 14 who received an anti-PD-1 checkpoint blockade agents off protocol, with no toxicity n = 19 mesothelioma patients (13 with anti-PD-1), 2 CRs (at 60 and 32 weeks), 5 PR, and 4 SD
Aurora with Baylor	HER2 scFv.CD28.ζ (AU101)	Phase I NCT00902044	Sarcoma	Without preconditioning	Ahmed et al. [113] n = 19, 1 PR Cell persistence for up to 18 months after infusion 3 patients outlived the median survival historic control with a survival of around 3 years 90% of the tumor biopsied after treatment were necrotic
				With CyFlu preconditioning	Results presented at ASCO 2017 [130] and AACR 2019 [114] n = 10, 2 CR, 3 SD 1 CR relapsed after 12 months, was reinjected, and is still in remission after 17 months; the other CR patient has been in remission for 32 months
	HER2 scFv.CD28.ζ in CMV.pp65 T cells (AU105)	Phase I NCT01109095	Glioblastoma multiforme	Bi-specific CAR-T (CMV-specific cytotoxic T cells) without preconditioning	Results presented at SITC 2015 [115] n = 17 (16 evaluable). 8 OR (1 PR, 7 SD for > 6 weeks, 8 PD) 3 patients in FU up to 30 months Median survival: 11.6 months from infusion and 24.8 months from diagnosis HER2 CMV T cells were detected in the peripheral blood for up to 12 weeks post-infusion
Autolus	GD2 scFv.CD28.ζ (1RG-CART)	Phase I NCT02761915	Neuroblastoma	With CyFlu	Results presented at AACR 2018 [116] No clinical responses were seen in first 12 patients but response in many sites of bone/marrow disease for 1 patient
Bellicum Pharmaceuticals	PSCA scFv.CD28.ζ (BPX-601)	Phase I/II NCT02744287	Pancreatic, gastric and prostate Adenocarcinoma	GoCAR®-separate inducible switch MyD88/CD40	Results presented at ESMO 2018 [117] n = 12 (9 evaluable). 5 SD, 4 PD 2 patients with SD had tumor shrinkage >  20%
CARsgen Therapeutics	Claudin 18.2 scFv.CD28.ζ CAR	Phase I NCT03159819 NCT03874897	Gastric and pancreatic adenocarcinoma	Multiple infusions	Results presented at ASCO 2019 [118] n = 12 (11 evaluable). 1 CR, 3 PR, 5 SD
	GPC3 scFv.CD28.ζ	Phase I NCT02876978 NCT03146234 NCT02395250	Lung squamous cell carcinoma HCC	With or without preconditioning	Results presented at ASCO 2017 [119] n = 13 (HCC, 11 evaluable). 1 PR, 3 SD, 2 PD
Cellular Biomedicine Group	EGFR scFv.4.1BB.ζ	Phase I/II NCT01869166	Biliary tract cancers and NSCLC	With or without preconditioning	Guo et al. [120] and Feng et al. [121] n = 17 biliary tract. 1 CR, 10 SD. Median PFS 4 months n = 11 NSCLC. 2 PR and 5 SD for 2–8 months Analysis of data indicated that the enrichment of Tcm in the infused CAR-T–EGFR cells improved the clinical outcome
Celyad	NKG2D ligands NKG2D.ζ (CYAD-01)	Phase I [122] NCT03018405	Colorectal cancer, epithelial ovarian and fallopian tube carcinoma, urothelial carcinoma, TNBC, and pancreatic cancer	Multiple IV infusions without prior preconditioning	Results presented at SITC 2018 [111] n = 14. 4 SD (3 mCRC + 1 OVA)
			Colorectal cancer	Single IV infusion with prior CyFlu preconditioning	Preliminary results presented at SITC 2018 [111] n = 2. Not yet evaluable
		Phase I NCT03310008	mCRC	Multiple IV infusions with concurrent FOLFOX chemotherapy regimen	Results presented at SITC 2018 [111] n = 3. 1 PR
		Phase I NCT03370198	mCRC	Loco-regional infusion into the hepatic artery	Not disclosed
	NKG2D ligands NKG2D.ζ (CYAD-101)	Phase I NCT03692429	mCRC	Multiple IV infusions with concurrent FOLFOX chemotherapy of an allogeneic CAR product (modified with a TCR inhibitory molecule)	Not disclosed yet
Eureka Therapeutics	AFP Second generation (ET-1402L1)	Phase I NCT03349255	Hepatocellular carcinoma and liver cancer	TCR-mimic scFv to target an AFP-peptide/HLA-A2 complex on HCC cancer cells	Results presented at CAR-TCR Summit 2018 [123] n = 6. 1 CR and 2 PR
Kite Pharma/Gilead	EGFRvIII scFv.CD28.ζ	Phase I/II NCT01454596	Malignant gliomas	With CyFlu preconditioning + IV IL-2	Not disclosed yet
Juno/Celgene	CD171 scFv.4-1BB.ζ (JCAR023)	NCT02311621	Neuroblastoma and ganglioneuroblastoma		Not disclosed yet
	MUC16 scFv.CD28.ζ (JCAR020)	NCT02498912	Ovarian cancer	IL-12-secreting CAR-T, IV or IP administered	Not disclosed yet
	ROR-1 scFv.4-1BB.ζ (JCAR024)	NCT02706392	TNBC and NSCLC		Results presented at AACR 2018 [124] and San Antonio Breast Cancer Symposium 2018 [125] n = 5. 4 MR with decreased disease burden patients (2 NSCLC; 2 TNBC), 1 SD (TNBC) for at least 56 days after second infusion n = 4 TNBC. 2 SD up to 19 weeks after first CAR-T infusion. 1 PR after second infusion for 14 weeks
Leucid Bio	ErbB dimers (HER2, 3 and EGFR) scFv.CD28.ζ (T4 CAR-Ts or LEU-001)	NCT01818323	Head and neck squamous cell carcinoma	Co-expression of a chimeric cytokine receptor (4αβ) which converts the IL-4 signal into a strong and selective growth signal Without prior preconditioning [108, 109] Intratumoral administration	Results presented at the CAR-T Congress EU in January 2019 n = 15. 9 SD 1 CR for 2.5 years after subsequent treatment with anti-PD-1 inhibitor pembrolizumab
Mustang Bio	HER2	NCT03389230	Glioblastoma and recurrent glioma		Not disclosed yet
		NCT03696030	Metastatic malignant neoplasm in the brain	Loco-regional administration	Not disclosed yet
	IL-13Rα2 scFv.4-1BB.ζ (MB101)	NCT02208362	Malignant glioma and brain neoplasms	Intracavitary infusions	Brown et al. [101] n = 1. 1 CR of 7.5 months
Novartis with University of Pennsylvania	Mesothelin scFv.4-1BB.ζ	NCT02159716	Metastatic pancreatic cancer, ovarian cancer, or malignant epithelial pleural mesothelioma		Not disclosed yet
	EGFRvIII-scFv.4-1BB.ζ	NCT02209376	Residual or recurrent glioma		First results indicated a good safety profile and first efficacy results were mixed as a result of high heterogeneity of tumor expression and adaptive TME, suggesting the need for a combination with PD-L1 evaluated in another study (NCT03726515).
		NCT03726515			Not disclosed yet
Sorrento Therapeutics	CEA-CAM5 (T-001)	NCT02349724	Lung, colorectal, gastric, breast, and pancreatic cancers		Not disclosed yet
		NCT03682744	Peritoneal carcinomatosis and metastases, colorectal, gastric, breast and pancreatic cancers	Loco-regional administration	Not disclosed yet
		NCT03818165	Pancreatic carcinoma	Loco-regional administration	Not disclosed yet.
		NCT02850536 HITM-SURE	Liver metastases	Loco-regional administration via the hepatic artery or splenic vein using the surefire infusion system	Results presented at SITC 2018 [126] n = 5 (4 with pancreatic cancer). 2 patients with no viable liver metastases by PET scan after treatment for up to 12 months Median OS post-treatment was 8.3 months with a mean OS of 9.8 months
		NCT01373047 HITM		Delivered into the hepatic circulation + systemic IL-2	Katz et al. [127] n = 9. 1 SD, OS: 4.5 months with 1 patient still alive at 23 months
		NCT 02416466 HITM-SIR		Hepatic artery infusions and yttrium-90 SIR-spheres	Results presented at AACR 2017 [128] n = 6. 3 SD, median OS 6.9 months

AACR American Association for Cancer Research, AFP α-fetoprotein, ASCO American Association of Clinical Oncology, CAR chimeric antigen receptor, CAR-T chimeric antigen receptor-T cell, CD cluster of differentiation, CEA carcinoembryonic antigen, CEA-CAM5 Carcinoembryonic antigen-related cell adhesion molecule 5, CMV cytomegalovirus, CR complete response, CyFlu non-myeloablative preconditioning chemotherapy composed of cyclophosphamide and fludarabine, EGFR epidermal growth factor receptor, EGFRvIII variant III of the epidermal growth factor receptor, ESMO European Society for Medical Oncology, GD2 disialoganglioside, GPC3 glypican 3, FOLFOX leucovorin [folinic acid], 5-fluorouracil, and oxaliplatin, FU follow-up, HCC hepatocellular carcinoma, HER2 human epidermal growth factor receptor 2, HLA human leukocyte antigen, HITM hepatic immunotherapy for metastases, HITM-SIR HITM with selective internal radiation therapy, HITM-SURE HITM with surefire infusion system, IL interleukin, IL-13Rα2 interleukin-13 receptor α2, IP intraperitoneal, IV intravenous, mCRC metastatic colorectal cancer, MR mixed response, MSKCC Memorial Sloan Kettering Cancer Center, MUC16 mucin 16, MyD88 myeloid differentiation primary response 88, OS overall survival, NKG2D natural killer group 2 member D, NSCLC non-small cell lung cancer, OR objective response, OVA ovarian cancer, PD-1 programmed death 1, PD-L1 programmed death-ligand 1, PET positron emission tomography, PFS progression-free survival, PR partial response, PSCA prostate stem cell antigen, ROR-1 receptor tyrosine kinase-like orphan receptor 1, scFv single-chain variable Fragment, SD stable disease, SITC Society for Immunotherapy of Cancer, Tcm central memory T cells, TCR T cell receptor, TME tumor microenvironment, TNBC triple-negative breast cancer