A Phase Ib/II Clinical Study Evaluating HMPL-453 Tartrate as Monotherapy and in Combination With Chemotherapy or Toripalimab in Advanced Solid Tumors

A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of HMPL-453 Tartrate as Monotherapy and in Combination With Chemotherapy or Toripalimab in Patients With Advanced Solid Tumors

A Phase Ib/II Clinical Study Evaluating HMPL-453 Tartrate as Monotherapy and in Combination with Chemotherapy or Toripalimab in Advanced Solid Tumors

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: HMPL-453; Drug: gemcitabine and cisplatin; Drug: toripalimab; Drug: Docetaxel

Detailed 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 monotherapy or combination therapy.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dose escalation phase of HMPL-453 monotherapy or combination therapy; HMPL-453 monotherapy or combination therapy	Drug: HMPL-453; HMPL-453 administered orally.; Drug: gemcitabine and cisplatin; Gemcitabine and Cisplatin administered intravenously.; Drug: toripalimab; Toripalimab administered intravenously.
Experimental: indication specific dose expansion phase of HMPL-453 monotherapy or combination therapy; HMPL-453 monotherapy or combination chemotherapy, in patients with IHCC, G/GEJ, UC, and solid tumors harboring specific FGFR gene alterations	Drug: HMPL-453; HMPL-453 administered orally.; Drug: gemcitabine and cisplatin; Gemcitabine and Cisplatin administered intravenously.; Drug: toripalimab; Toripalimab administered intravenously.; Drug: Docetaxel; Docetaxel administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability(Incidence and severity of adverse events (AEs))	DLT, TEAEs and SAEs	6 months after the last patient enrolled
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
disease control rate (DCR)	The incidence of complete response, partial response and stable disease	up to 2 years
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
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
overall survival (OS)	The period from date of enrollment to date of death	up to 2 years

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2022
• Primary Completion (Actual): July 17, 2025
• Study Completion (Actual): January 17, 2026

Study Registration Dates

• First Submitted: October 31, 2021
• First Submitted That Met QC Criteria: December 10, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HMPL-453, FGFR, PD-1,IHCC, ICC, gastric cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Docetaxel; Gemcitabine; Cisplatin; toripalimab
• Other Study ID Numbers: 2021-453-00CH1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No