Delving into the Latest Updates on VC-004 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

TrkA

Mechanism

TrkA antagonists(Nerve growth factor receptor Trk-A antagonists)

Therapeutic Areas

NeoplasmsInfectious DiseasesNervous System Diseases+ [1]

Active Indication

Locally Advanced Malignant Solid NeoplasmMetastatic Solid TumorSolid tumor+ [4]

Inactive Indication-

Originator Organization

Jiangsu Vcare PharmaTech Co., Ltd.

Active Organization

Jiangsu Vcare PharmaTech Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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BACKGROUND AND OBJECTIVEVC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004.METHODSThe study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests.RESULTSThe maximum plasma concentration (C_max) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to C_max (T_max) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of C_max, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC_0-t), and AUC from zero to infinity (AUC_0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study.CONCLUSIONSThe intake of high calorie food decreased the absorption rate and increased the T_max of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner.TRIAL REGISTRATIONClinicalTrials.gov ID: NCT055528120.

01 Jan 2024·Lung Cancer

ETV6::NTRK3 gene fusion in a patient with metastatic lung atypical carcinoid successfully treated with repotrectinib: A case report

Author: Ai, Xinghao ; Gao, Lin ; Lu, Shun

INTRODUCTIONChromosomal rearrangements involving the neurotrophin kinase (NTRK) genes NTRK1, NTRK2 and NTRK3 with different fusion partners occur in non-small cell lung cancers (NSCLCs) and other solid tumors. Novel NTRK rearrangement-related tumors are still being discovered.METHODSHerin, we describe a male patient with a mass in the left upper lobe that was biopsied by bronchoscopy. This case was diagnosed with stage Ⅳ lung atypical carcinoid (AC) harboring the ETV6::NTRK3 gene fusion.RESULTSHe received 1st line treatment with everolimus lasting for 4 months. After chemotherapy failure, he received 3rd treatment with VC004 in a phase 1/2 study and achieved stable disease, but he stopped taking it due to intolerance. He subsequently received repotrectinib treatment and achieved a partial response of more than ten months.CONCLUSIONSTo the best of our knowledge, we reported the first case demonstrating anti-tumor activity of repotrectinib in a patient with AC carring an ETV6-NTRK3 gene fusion, indicating that repotrectinib may be an efficient therapeutic option for tumors with NTRK gene rearrangements.

01 Jan 2000·SynapseQ4 · MEDICINE

Preclinical testing of N-[11c]-methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate, a novel radioligand for detection of cerebral muscarinic receptors using PET

Q4 · MEDICINE

Article

Author: Willem Vaalburg ; Theodora Wegman ; Thomas Jakob Visser ; Petra Doze ; Aren Van Waarde

The muscarinic antagonist N-[(11)C]methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate (VC-004) 1 was tested for visualization of muscarinic receptors in the brain. The active (R)-isomer (pKb = 10.92) was labeled by reacting [(11)C]-CH(3)I with the secondary amine precursor (40-60% decay-corrected radiochemical yield, specific activity 13.0-34.3 TBq/mmol, 45 min after end of bombardment). Biodistribution studies were performed in male Wistar rats. Brain uptake of (R)-[(11)C]-VC-004 was high, standard uptake values (SUVs) ranging from 1.6 in cerebellum to 3.3 in frontal cortex. In all brain regions, the nonsubtype selective muscarinic antagonist scopolamine (2.5 mg/kg) blocked (R)-[(11)C]-VC-004 binding to the same extent (84.6 +/- 3.3%) as nonlabeled (R)-VC-004 (2.0 mg/kg, 83.2 +/- 4.6%). In contrast, the fraction of [(11)C]VC-004 binding which was blocked by atropine (2.5 mg/kg) was significantly smaller (54 +/- 17%). The reduction of (R)-[(11)C]-VC-004 binding by low-dose atropine (0.5 mg/kg) was not significantly different from that caused by (R)-(-)-QNB (20 microg/kg). The decrease in specific binding of (R)-[(11)C]VC-004 after (R)-(-)-QNB block correlated well with literature values for the percentages of M(2) receptors in the brain regions studied. (R)-[(11)C]VC-004 was rapidly cleared from plasma (92% with a half-life of 0.27 min) and the fraction of total plasma radioactivity representing parent compound decreased from 99% to 42% at 10 min postinjection. Although (R)-[(11)C]VC-004 can visualize muscarinic receptors in the brain, it does not show selectivity for the M(2)-subtype. A low dose (0.5 mg/kg) of atropine seems to preferentially block M(2)-receptors in vivo, as has been reported for (R)-(-)-QNB.

100 Deals associated with VC-004

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Malignant Solid Neoplasm	Phase 3	CN	Jiangsu Vcare PharmaTech Co., Ltd.	20 Nov 2024
Metastatic Solid Tumor	Phase 2	CN	Jiangsu Vcare PharmaTech Co., Ltd.	20 Nov 2020
Solid tumor	Phase 2	CN	-	20 Nov 2020
NTRK fusion-positive solid tumors	Phase 1	CN	Jiangsu Vcare PharmaTech Co., Ltd.	20 Oct 2022
Cancer Pain	IND Approval	CN	Jiangsu Vcare PharmaTech Co., Ltd.	16 Aug 2023
inflammatory dermatosis	IND Approval	CN	Jiangsu Vcare PharmaTech Co., Ltd.	22 May 2023
Pruritus	IND Approval	CN	Jiangsu Vcare PharmaTech Co., Ltd.	22 May 2023