Reference Detail

Ref Type

Journal Article

PMID

(38037839)

Authors

Ouyang Q, Wang Y, Zhang J, Wu Q, Wei H, Li C, Qian X, Hu X

Title

HS-10352 in hormone receptor-positive, HER2-negative advanced breast cancer: A phase 1 dose-escalation trial.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer medicine	12	24	2023 Dec	21849-21860	Cancer Med

URL

Abstract Text

Approximately 40% of patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) exhibit PIK3CA mutations.This study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS-10352, a selective PI3Kα inhibitor, in this patient population.Conducted as a phase 1 dose-escalation trial, HS-10352 was administered orally once-daily (QD) at dose levels of 2, 4, 6, and 8 mg. The primary endpoints were dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). This study is registered at ClinicalTrials.gov (NCT04631835).Between August 2020 and March 2022, a total of 18 female patients were enrolled. DLT, manifested as hyperglycemia, occurred in two patients in the 8 mg QD group, establishing an MTD of 6 mg QD. The most common treatment-related adverse events were hyperglycemia (88.9%) and weight loss (61.3%). In the 6 mg QD group, four patients (66.7%) had a partial response (PR), and one (16.7%) had stable disease (SD). Among the four patients with PIK3CA mutated tumors in this dosage group, three (75.0%) had PR and one (25.0%) had SD. The median progression-free survival was not reached (95% confidence interval, 11.1-NA).HS-10352 at 6 mg QD was well-tolerated in patients with HR-positive, HER2-negative ABC, and showed preliminary antitumor activity in patients with PIK3CA mutated tumors. These findings support the further clinical development of HS-10352.

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Molecular Profile	Treatment Approach
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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
HS-10352	HS-10352	5	0

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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
HS-10352		HS10352\|HS 10352	PIK3CA inhibitor 26	HS-10352 inhibits PIK3CA, which potentially results in decreased tumor cell proliferation and reduced tumor growth (PMID: 38037839).

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA E542K	Her2-receptor negative breast cancer	predicted - sensitive	HS-10352	Case Reports/Case Series	Actionable	In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835).	38037839
PIK3CA E545D	Her2-receptor negative breast cancer	predicted - sensitive	HS-10352	Case Reports/Case Series	Actionable	In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835).	38037839
PIK3CA E545K	Her2-receptor negative breast cancer	predicted - sensitive	HS-10352	Case Reports/Case Series	Actionable	In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835).	38037839
PIK3CA H1047L	Her2-receptor negative breast cancer	predicted - sensitive	HS-10352	Case Reports/Case Series	Actionable	In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835).	38037839
PIK3CA H1047R	Her2-receptor negative breast cancer	predicted - sensitive	HS-10352	Case Reports/Case Series	Actionable	In a Phase I trial, HS-10352 treatment resulted in an objective response rate (ORR) of 27.8% (5/18, all partial responses), disease control rate (DCR) of 55.6%, and median progression-free survival (mPFS) of 3.9 mo in HR-positive, ERBB2 (HER2)-negative advanced breast cancer patients overall, and in the 6mg group led to an ORR of 66.7% and DCR of 83.3%, with an ORR of 75.0% (3/4) and DCR of 100% in patients with PIK3CA mutations (E542K, E545K, E545D, H1047L, H1047R) (PMID: 38037839; NCT04631835).	38037839

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