Clinical Development of TargomiRs, a miRNA Mimic-Based Treatment for Patients with Recurrent Thoracic Cancer

Figures & data

Figure 1.  Swimmers plot of the first six patients treated with TargomiRs.

Figure 2.  Computed tomography scans from patient 5 before (left) and after 8 weeks (right) of TargomiR treatment, showing a partial response.

Reprinted with permission from [39] © American Thoracic Society (2016).

Table 1.  Preclinical studies of miRNA mimics in lung cancer and mesothelioma.

Tumor	miRNA	Delivery	Results	Ref.
NSCLC	Let-7b	Adenovirus Cationic lipid, it. Lentivirus NLE, iv.	Reduced xenograft growth; 66% reduction in orthotopic tumor burden Decreased tumor growth 75% reduction in tumor burden Reduced orthotopic tumor burden	[18] [12] [20]
NSCLC	miR-34	Cationic lipid, it. and iv. NLE, iv.	Decreased xenograft growth 60% reduction in orthotopic tumor burden	[13] [20]
NSCLC	miR-200c	Amphoteric liposome	miR-200c plus radiotherapy delayed xenograft growth	[22]
NSCLC	miR-29b	Liposomes, iv.	60% smaller xenografts	[21]
NSCLC	Let-7b and miR-34a	NLE, iv. Amphoteric liposome, iv.	Decreased orthotopic tumor burden with combination 40% increased survival with combination or miR-34a alone	[23] [23]
MPM	miR-16	EDVs, iv.	Dose-dependent inhibition of xenograft growth	[10]
MPM	miR-34b/c	Adenovirus, it.	55% sc. xenograft growth inhibition	[30]
MPM	miR-193a-3p	EDVs, iv.	70% sc. xenograft growth inhibition	[29]
MPM/NSCLC	Consensus mimics	EDVs, iv.	60–80% sc. xenograft growth inhibition	[32]

EDV: EDV™nanocells; iv.: Intravenous; it.: Intratumoral; MPM: Malignant pleural mesothelioma; NLE: Neutral lipid emulsion; sc.: Subcutaneous.

Table 2.  Toxicities following TargomiR administration in the first six-patent cohort.

Clinical parameters	Patient
	1	2	3	4	5	6
Gender/age	M/78	F/61	M/52	M/74	M/53	F/68
Pretreatment	CT (2 lines) and RT	CT (two lines)	CT (two lines) and RT	CT (two lines)	CT (two lines)	Chemotherapy four lines
Toxicity (CTCAE Version 4)	Chills and rigor (G2) –	Chills and rigor (G2) Pain at tumor site (G3)	Rigor (G2) –	Rigor (G2) Pain at tumor site (G1)	Chills (G2) –	Pain at tumor site (G2) –
Laboratory	Lymphopenia (G4)	Lymphopenia (G4)	Lymphopenia (G4)	Lymphopenia (G4)	Lymphopenia (G3)	Lymphopenia (G3)
Overall quality of life	Stable	Slight improvement	Slight improvement	Stable	Major improvement	Stable
Response (modified RECIST) after 8 weeks	SD	SD	SD	PD (+ second primary)	PR (confirmed)	SD (PR not confirmed)
Treatment duration	8 weeks	9 weeks	16 weeks	8 weeks	40 weeks	42 weeks

CT: Chemotherapy; F: Female; G: Grade; M: Male; PD: Progressive disease; PR: Partial response; RT: Radiotherapy; SD: Stable disease.

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