HMPL-453 (FGFR Inhibitor) in Combination With Chemotherapy or Anti-PD-1 Antibody in Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of HMPL-453 (FGFR Inhibitor) Combined With Chemotherapy or Anti-PD-1 Antibody in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05173142
• Other study ID #: 2021-453-00CH1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 22, 2022
• Est. completion date: August 2025

Study information

• Verified date: March 2022
• Source: Hutchison Medipharma Limited
• Contact: Min Ling, Bachelor
• Phone: +86 021-20671959
• Email: minl[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase Ib/II clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of HMPL-453 combined with chemotherapy or anti-PD-1 antibody in patients with advanced solid tumors.

Description:

The study includes a dose escalation phase and a dose-expansion phase.

Patients with advanced solid tumor will be enrolled in the dose escalation phase to assess the tolerability, safety, and PK profile of HMPL-453 monotherapy or combination therapy.

Patients with specific types of advanced or metastatic tumors harboring certain FGFR gene alterations will be enrolled in the dose expansion phase to assess the preliminary efficacy of HMPL-453 combination therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 141
• Est. completion date: August 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria

• Dose escalation phase: patients with histologically or cytologically confirmed locally advanced or metastatic solid tumor who progressed on or are intolerant of standard therapy;

• Dose expansion phase: patients with UC, GC/GEJ, or IHCC harboring specific FGFR gene alterations;

• Age 18 to 75 years;

• Those who are able to give written informed consent, and able to comply with protocol-specified visits and related procedures;

• Ability to swallow study drug;

• ECOG PS of 0 or 1;

• Measurable lesion according to RECIST v1.1, refer to the protocol;

• Adequate organ and bone marrow function;

• Life expectancy = 12 weeks;

• Female patients or male patients with partners of childbearing potential must take effective contraceptive measures per the protocol.

Exclusion Criteria

• Patients who previously received selective FGFR targeting therapy;

• Concurrent participation in another interventional clinical study, excluding those in the follow-up period and have not recently received investigational intervention;

• Current or previous history of central nervous system (CNS) metastases;

• Current or previous history of retinal detachment;

• Known history of primary immunodeficiency;

• Female patients who are pregnant or lactating;

• Patients who in the opinion of the investigator may be unsuitable for participating in the study;

• Patients with acute or chronic active hepatitis B or C infection;

• Known human immunodeficiency virus (HIV) infection and syphilis infection;

• Clinically significant cardiovascular disease such as congestive heart failure or arrhythmia;

• Uncontrolled hypertension despite optimal medical management;

• Received live vaccine within 30 days before the first dose of study drug(s);

• Those who have undergone major surgical procedures (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to the first study treatment or who are expected to be in need of major surgery; those with unhealed wounds, ulcers or fractures.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• HMPL-453
HMPL-453 administered orally.
• gemcitabine and cisplatin
Gemcitabine and Cisplatin administered intravenously.
• toripalimab
Toripalimab administered intravenously.
• Docetaxel
Docetaxel administered intravenously.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability(Incidence and severity of adverse events (AEs))	DLT, TEAEs and SAEs	6 months after the last patient enrolled
Primary	Preliminary efficacy/Objective response rate (ORR)	Objective response rate (ORR) in patients with the selected tumors along with certain FGFR gene alterations	up to 2 years
Secondary	Efficacy/Progression-free survival (PFS)	the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).	up to 2 years
Secondary	disease control rate (DCR)	The incidence of complete response, partial response and stable disease	up to 2 years
Secondary	time to response (TTR)	The period from the date of enrollment to the date when the criteria for complete response or partial response was first measured (first record shall prevail).	up to 2 years
Secondary	duration of response (DoR)	The duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded	up to 2 years
Secondary	overall survival (OS)	The period from date of enrollment to date of death	up to 2 years