A Study of HS269 in Patients With Advanced Solid Tumors

NCT05058352 | Unknown Phase 1

• 1 other identifier: HS269-Ⅰ-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, open-label, first in human study of HS269 tablet, a small molecule highly-selective RET Inhibitor. The dose-escalation study will assess the safety, tolerability, and pharmacokinetics of HS269 and determine the dose and schedule to be used in Phase II. Seventeen to thirty-six patients with advanced solid tumor may be enrolled in this study.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicities (DLT)

  Incidence rate of dose limiting toxicities (DLT)

  From date of initial dose until up to 33 days for treatment

• Adverse Event(s) and Serious Adverse Event(s)

  The occurrence and rate of AE and SAE

  Through study completion or early study discontinuation（up to 12 months）

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax)

  From date of initial dose until up to 33 days for treatment

• Area Under the Plasma Concentration versus Time Curve (AUC)

  From date of initial dose until up to 33 days for treatment

• Calcitonin in Peripheral Blood

  Through study completion or early study discontinuation（up to 12 months）

• Thyroglobulin in Peripheral Blood

  Through study completion or early study discontinuation（up to 12 months）

• ORR

  Approximately 12 months

Study Arms (1)

HS269

EXPERIMENTAL

Multiple doses of HS269 tablets

Drug: HS269

Interventions

HS269 DRUG

Oral tablets, once daily. Dose escalation from 50 mg QD, through 100 mg, 200mg, 300 mg, 400 mg, to 500mg.

HS269

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years, no gender limit.
• Patients with advanced solid tumors confirmed by histology or cytology fail to receive standard treatment, or there is no standard treatment, or standard treatment is not applicable at this stage.
• At least one evaluable tumor lesion according to RECIST version 1.1.
• ECOG≤ 1.
• The estimated survival time was more than 3 months.
• The function of all organs was good, the specific indexes were as follows:
• Blood system (no transfusion or hematopoietic stimulating factor treatment within 14 days) i. #NEUT ≥1.5×109/L ii. PLT ≥90×109/L iii. HGB ≥85g/L Liver function i. TBIL ≤1.5×ULN ii. ALT ≤3×ULN; Patients with liver metastasis or liver cancer: ≤ 5 × ULN iii. AST ≤3×ULN; Patients with liver metastasis or liver cancer: ≤ 5 × ULN Renal function i. Ccr \>50 ml/min（According to Cockcroft-Gault formula） Blood coagulation function i. APTT ≤1.5×ULN ii. INR ≤1.5×ULN
• The subjects should be informed and agreed to the study before the start of the trial, and sign the written informed consent voluntarily.

You may not qualify if:

• Received anti-tumor treatments within 14 days or less than 5 half-lives (whichever is longer) before the first use of the study drug
• Received blood transfusion, erythropoietin, recombinant human thrombopoietin or colony stimulating factor and other treatments within 7 days before receiving blood system examination during the screening period.
• Received other unmarketed clinical study drugs or treatments within 4 weeks before the first use of the study drug.
• Major organ surgery (excluding biopsy) or significant trauma occurred within 4 weeks before the first use of the study drug;
• Systemic administration of glucocorticoids (prednisone \> 10 mg / day or equivalent dose of the same drug) or other immunosuppressants within 14 days before the first use of the study drug; except for local, eye, intra articular, nasal and inhaled corticosteroids; short-term use of glucocorticoids for preventive treatment (e.g. prevention of contrast agent allergy)；
• CYP1A2/P-gp potent inhibitors or potent inducers were used within 7 days before the first use of the study drug；
• Resistance to selective RET inhibitors;
• The adverse reactions of previous anti-tumor therapy have not yet recovered to CTCAE 5.0 grade evaluation ≤ 1 (except for the toxicity without safety risk judged by researchers such as alopecia)；
• Patients with central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence indicating that the central nervous system metastasis or meningeal metastasis has not been controlled, which is not suitable for the study.
• Have active infection and need systemic anti infection therapy；
• Have a history of immunodeficiency, including HIV antibody test positive；
• Active hepatitis B, allowing preventive antiviral treatment other than interferon; hepatitis C virus infection；
• Present or past interstitial lung disease (except radiation-induced pulmonary fibrosis without hormone therapy)；
• Poorly controlled diabetic patients.
• Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Zhejiang Hisun Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, China

Location

Study Officials

• Qiming Wang

  Henan Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Qi Dang

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caicun Zhou

CONTACT

021-65115006; caicunzhoudr@163.com

Wei Li

CONTACT

021-65115006; leewluck@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 27, 2021
• Study Start: October 1, 2021
• Primary Completion: October 1, 2022
• Study Completion: April 1, 2023
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

CN (1)