A Study of HMPL-415S1 in Patients With Advanced Malignant Solid Tumors
ConditionAdvanced Malignant Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorHutchmed
About this trial
The objective of this study is to evaluate the safety, tolerability and PK profile of HMPL-415S1 and determine MTD and/or RP2D in patients with advanced malignant solid tumor.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Fully understand this study and voluntarily sign the ICF;
Dose escalation Patients with advanced malignant solid tumor confirmed by histopathology or cytology, who have failed, been intolerant or unavailable to, or have none standard treatment for various reasons; Dose expansion phase: Patients with advanced malignant solid tumor confirmed by histopathology or cytology, who have failed, been intolerant or unavailable to, or have none standard treatment for various reasons, carrying aberrant activating mutations in the KRAS pathway；
Presence of at least one measurable lesion (RECIST 1.1 criteria);
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 point;
Disqualifiers
Patients who priorly received SHP2 inhibitors;
Receiving the approved systemic antitumor treatment within 4 weeks prior to the first dose, including: chemotreatment, targeted treatment, immunization treatment, biological treatment, etc. (wash-out for 2 weeks for hormone treatment or traditional chinese medicine and chinese patent medicine with clear antitumor indications);
Have been in the treatment period of other interventional clinical studies (including small molecule chemicals and large molecule antibodies) within 4 weeks prior to the first dose. If participating in a non-interventional clinical study (eg, epidemiological study), you can enroll in this study; if already in the survival follow-up period of an interventional clinical study, you can enroll in this study.
Major surgery or radical radiotreatment (except palliative radiotreatment for metastases to bone lesions) within 4 weeks prior to first dose.
Trial design
Design model
Single group
Treatments tested in this trial
HMPL-415S1
DrugHMPL-415S1 will be supplied as 0.5 mg, 5 mg and 25 mg capsules
Treatment groups
81 Participants
are divided into 1 treatment groupGroup A: HMPL-415S1Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or RP2D of HMPL-415S1 as a single oral agent in advanced malignant solid tumor
Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period
Time frame
from Cycle 0Day1 up to Cycle1Day28 (each cycle is 28 days).Secondary outcomes
1
To investigate the pharmacokinetic (PK) profile of oral HMPL-415S1
Plasma peak concentration of HMPL-415S1 (Cmax).
Time frame
from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).2
AUCinf (Cycle 0 ) of HMPL-415S1
AUCinf: area under the concentration vs. time curve from zero to infinity after single (first)dose.
Time frame
from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).3
AUC(0-tlast) (Cycle 0 ) of HMPL-415S1
AUC from time zero to the last data point.
Time frame
from pre-dose to day 5 of cycle 0. (cycle 0 contains 5 days).4
Objective Response Rate (ORR)
Percentage of patients with Complete Response(CR) or Partial Response(PR) as the best response evaluated in accordance with RECIST 1.1.
Time frame
From baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 3 years). Source ClinicalTrials.gov