HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HS-20117 as a monotherapy for participants with advanced solid tumors.
This is a multicenter, open-label, Phase I clinical study of HS-20117 to evaluate the safety, tolerability, PK, immunogenicity and efficacy in participants with advanced solid tumors. The study consists of phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 in participants with locally advanced or metastatic NSCLC who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy with EGFR exon 20 insertion mutations, and to explore the efficacy of HS-20117 in participants with other advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
322
Phase Ia: patients will receive HS-20117 starting at 400 mg, and subsequent cohorts will test escalating doses, if tolerated, until a maximum tolerated dose (MTD) or maximum applicable dose (MAD) is defined. Phase Ib: patients will receive HS-20117 at MED or MAD
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, China
[Phase 1a] Maximum tolerated dose (MTD) of HS-20117
MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT.
Time frame: Cycle 1 (28 days)
[Phase 1a] Maximum applicable dose (MAD) of HS-20117
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: Cycle 1 (28 days)
[Phase 1b] 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 until the date of disease progression or withdrawal from study, approximately 2 years
[phase 1a and 1b] Incidence 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: From the date of first dose until 90 days after the final dose. A cycle is 28 days
[phase 1a and 1b] PK parameters: Maximum serum concentration (Cmax) of HS-20117
The Cmax is the maximum observed serum concentration of HS-20117.
Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
[phase 1a and 1b] PK parameters: Trough serum concentration (Ctrough) of HS-20117
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Ctrough is the observed serum concentration immediately prior to the next administration.
Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
[phase 1a and 1b] 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 until 30 days after the final dose. A cycle is 28 days
[phase 1a] 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 until 30 days after the final dose. A cycle is 28 days.
[phase 1a] PK parameters: Terminal elimination half-life (t1/2) of HS-20117
The t1/2 is defined as the time it takes for the concentration levels to fall to 50% of their value.
Time frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
[phase 1a] Efficacy of HS-20117: 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 until the date of disease progression or withdrawal from study, approximately 2 years.
[phase 1a and 1b] 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 until the date of disease progression or withdrawal from study, approximately 2 years.
[phase 1a and 1b] 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.
Time frame: From the date of CR, PR until the date of disease progression or death, approximately 2 years.
[phase 1a and 1b] 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 randomization or first dose (if randomization is not needed) until the date of disease progression or death, approximately 2 years.
[phase 1b] 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 randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years
[phase 1a and 1b] Immunogenicity of HS-20117
Immunogenicity will be measured by the number of participants that are ADA positive.
Time frame: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).