British Journal of Cancer: Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation agents
July 30 2024 - 8:30PM
Business Wire
InnoCare announced British Journal of Cancer, part of leading
science journal Nature, recently published a paper entitled
"Zurletrectinib is a next-generation TRK inhibitor with strong
intracranial activity against NTRK fusion-positive tumors with
on-target resistance to first-generation agents". The journal
concluded that zurletrectinib is a novel, highly potent
next-generation TRK inhibitor with higher in vivo brain penetration
and stronger intracranial activity than other next-generation
agents.
The paper pointed out that zurletrectinib displayed strong
potency against TRKA, TRKB, and TRKC WT kinases, as well as
acquired resistance mutations TRKA G595R and TRKA G667C.
Zurletrectinib was more active than other FDA approved or
clinically tested first generation (larotrectinib) and
next-generation (selitrectinib and repotrectinib) TRK inhibitors
against most TRK inhibitor resistance mutations. Similarly,
zurletrectinib (1 mg/kg BID) inhibited tumor growth in xenograft
models derived from NTRK fusion-positive cells at a dose 30 times
lower when compared to selitrectinib.
The paper further demonstrated that, in a central nervous system
(CNS) penetrant pharmacokinetic study in SD rats, zurletrectinib
showed improved ability to penetrate the blood-brain barrier,
reaching the brain more effectively than selitrectinib and
repotrectinib. Zurletrectinib's increased brain penetration was
also translated into improved antitumor activity. In an orthotopic
mouse glioma xenograft model carrying the TRKA G598R/G670A
resistance mutation, zurletrectinib (15 mg/kg) significantly
improved the survival of mice harboring orthotopic NTRK
fusion-positive, TRK-mutant gliomas (median survival = 41.5, 66.5,
and 104 days for selitrectinib, repotrectinib, and zurletrectinib
respectively; P < 0.05), showing superior efficacy compared to
repotrectinib (15 mg/kg) and selitrectinib (30 mg/kg) (P=0.0384 and
0.0022, respectively), with an excellent safety profile.
The corresponding authors of the paper are Dr. Alexander Drilon,
Department of Medicine, Memorial Sloan Kettering Cancer Center, New
York, NY, USA, and Dr. Emiliano Cocco, Department of Biochemistry
and Molecular Biology, University of Miami, Miller School of
Medicine, FL, USA. The first author is Paolo Roa, Department of
Biochemistry and Molecular Biology, University of Miami, Miller
School of Medicine, FL, USA. Full text can be found in
https://www.nature.com/articles/s41416-024-02760-1.
InnoCare is accelerating the registrational trial of
zurletrectinib in China. The clinical study with zurletrectinib has
covered NTRK fusion adult patients, adolescent patients and
pediatric patients. Zurletrectinib has demonstrated good efficacy
and safety profile, and overcome acquired resistance to the first
generation TRK inhibitors, bringing benefit to patients who failed
prior TRKi therapy.
About InnoCare
InnoCare (HKEX: 09969; SSE: 688428) is a commercial stage
biopharmaceutical company committed to discovering, developing, and
commercializing first-in-class and/or best-in-class drugs for the
treatment of cancer and autoimmune diseases with unmet medical
needs in China and worldwide. InnoCare has branches in Beijing,
Nanjing, Shanghai, Guangzhou, Hong Kong, and United States.
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Media Chunhua Lu 86-10-66609879
chunhua.lu@innocarepharma.com
Investors 86-10-66609999 ir@innocarepharma.com