Clinical trial NCT05173142: HMPL-453 (FGFR Inhibitor) in Combination With Chemotherapy or Anti-PD-1 Antibody in Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: HMPL-453, FGFR, PD-1,IHCC, ICC, gastric cancer
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2021-12-29
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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 combination therapy.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability(Incidence and severity of adverse events (AEs))
timeFrame: 6 months after the last patient enrolled
measure: Preliminary efficacy/Objective response rate (ORR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Efficacy/Progression-free survival (PFS)
timeFrame: up to 2 years
measure: disease control rate (DCR)
timeFrame: up to 2 years
measure: time to response (TTR)
timeFrame: up to 2 years
measure: duration of response (DoR）
timeFrame: up to 2 years
measure: overall survival (OS)
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
References: