HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity of HS-20117 in combination with other drugs in advanced solid tumors.
This is a multicenter, open-label, Phase Ib clinical trial of HS-20117 combination therapies to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity in participants with advanced solid tumors. The study includes a dose escalation part and a dose expansion part. The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 combination therapies in participants with advanced solid tumor. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 combination therapies in participants with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations or EGFR classical mutations, and RAS/BRAF V600E wild type CRC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
780
HS-20117 + HS-20093
HS-20117 + cisplatin/carboplatin + pemetrexed
HS-20117 + HS-20093 + 5-FU
Tianjin Medical University Cancer Institute & Hospital
Tianjin, China
RECRUITINGIncidence and severity of treatment-emergent adverse events
Adverse event (assessed according to NCI CTCAE v5.0) is defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: rom the date of first dose to 90 days after the final dose.
Tolerability of HS-20117 combination therapy: incidence of DLT events, maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-20117 in combination therapies.
MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT. MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored.
Time frame: From the date of first dose to day 21.
Efficacy of HS-20117: Objective response rate (ORR)
ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1
Time frame: From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
Efficacy of HS-20117: disease control rate (DCR)
DCR is defined as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks) per RECIST v1.1.
Time frame: From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
Efficacy of HS-20117: duration of response (DoR)
DoR only applies to participants whose best overall response is CR or PR based on assessment per RECIST v1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying disease.
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CAPOEX: Oxaliplatin+Capecitabine
FOLFIRI=Irinotecan+Leucovorin Calcium+5-FU
mFOLFOX6=Oxaliplatin+Leucovorin Calcium+5-FU
Time frame: From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
Efficacy of HS-20117: progression free survival (PFS)
PFS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. PFS will be assessed per RECIST v1.1.
Time frame: From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
Efficacy of HS-20117: overall survival (OS)
OS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of death due to any cause. For each participant who is not known to have died as of the cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
Time frame: From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
PK parameters: Trough serum concentration (Ctrough) of HS-20117 and HS-20093
Ctrough is the observed serum concentration immediately prior to the next administration.
Time frame: From the date of first dose to 90 days after the final dose.
PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117
The Tmax is defined as time to reach maximum observed serum concentration of HS-20117.
Time frame: From the date of first dose to 90 days after the final dose.
PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117
The AUCtau is defined as the area under the serum concentration-time curve during a dose interval time period (tau).
Time frame: From the date of first dose to 90 days after the final dose.
PK parameters: Maximum serum concentration (Cmax) of HS-20117 and HS-20093.
The Cmax is the maximum observed serum concentration of HS-20117, HS-20093.
Time frame: From the date of first dose to 90 days after the final dose.
Immunogenicity of HS-20117
Immunogenicity will be measured by the number of participants that are ADA positive.
Time frame: From the date of first dose to 90 days after the final dose.