Reference Detail

Ref Type

Journal Article

PMID

(38295954)

Authors

Shi Y, Hu X, Li X, Gong C, Wang K, Li Y, Zhang S, Luo Y, Wang P, Jiang L, Meng X, Dong X, Wang H, Yang R, Mei Q, Liu B, Yang L, Sun Y

Title

Ficonalkib (SY-3505) in Advanced ALK-Positive Non-Small-Cell Lung Cancer: A Multicenter, Open-Label, Single-Arm, Phase I/Ⅱ Study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer			2024 Jan 29		J Thorac Oncol

URL

Abstract Text

Treatment options for second-generation (2nd-gen) anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) resistant patients are limited. We evaluated the safety, pharmacokinetics, and efficacy of ficonalkib (SY-3505), a third-generation (3rd-gen) ALK TKI.This first-in-human, phase I/Ⅱ study (Chinese Clinical Trial Registry identifier: ChiCTR1900025619; ClinicalTrials.gov identifier: NCT05257512) had two parts. Phase I included a dose-escalation phase (25-800 mg quaque die [QD]) and a dose-expansion phase (500 mg QD or 600 mg QD). Phase Ⅱ enrolled patients treated at recommended phase Ⅱ dose (RP2D). Primary endpoints were safety in phase I and objective response rate (ORR) in phase Ⅱ.Between Apr 21, 2020, and Aug 31, 2023, a total of 127 patients were enrolled, with 62 in phase I. Ficonalkib was well absorbed and tolerated, with one dose limited toxicity event occurring at 800 mg QD. Treatment-related adverse events (TRAEs) occurred in 85.5% of patients, with 19.4% experienced ≥ grade 3 events. The ORR was 38.3% (23/60, 95% confidence interval [CI] 26.1-51.8%) in phase I, and 600 mg QD was established as RP2D. In phase Ⅱ, a total of 65 patients received ficonalkib at 600 mg QD. Totally 88 patients received ficonalkib at 600 mg QD in phase I/Ⅱ, and all had received prior 2nd-gen ALK TKI treatment. 90.9% of patients experienced TRAEs and 14.8% experienced ≥ grade 3 events. The ORR in efficacy-evaluable patients received ficonalkib at 600 mg QD was 47.5% (38/80, 95% CI 36.2-59.0%), with an intracranial ORR of 37.5% (12/32, 95% CI 21.1-56.3%) in these patients with measurable brain lesions at baseline.Ficonalkib (SY-3505) was well tolerated, with favorable safety profiles and promising efficacy in patients resistant to prior 2nd-gen ALK TKI.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Ficonalkib	Ficonalkib	2	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Ficonalkib		SY-3505\|SY3505\|SY 3505\|CT-3505\|CT3505\|CT 3505	ALK Inhibitor 32	Ficonalkib (SY-3505) is a third-generation ALK inhibitor with activity against wild-type and mutant ALK, which potentially inhibits tumor growth (PMID: 38295954).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - sensitive	Ficonalkib	Case Reports/Case Series	Actionable	In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), a disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 in Chinese patients with ALK-positive non-small cell lung cancer, with an ORR of 70% (7/10) in patients with ALK G1202R (PMID: 38295954; NCT05257512).	38295954
ALK rearrange	lung non-small cell carcinoma	sensitive	Ficonalkib	Phase Ib/II	Actionable	In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 months, and an intracranial ORR of 37.5% (12/32, 4 complete responses, 8 PR) and intracranial DCR of 100% (32/32) in Chinese patients with ALK-positive non-small cell lung cancer (PMID: 38295954; NCT05257512).	38295954