A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

Phase 3RecruitingNCT06417008

Hansoh BioMedical R&D Company1,080 enrolled

Overview

HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of this study is to assess the safety, efficacy, pharmacokinetics and immunogenicity of HS-20117 combined with Aumolertinib in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions \[Exon 19del\] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

This is a multicenter Phase Ib/III clinical study evaluating the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20117 in combination with aumolertinib in subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The study is divided into two phases, Phase Ib, a dose expansion study and Phase III, a confirmatory study. In the dose expansion phase (Phase Ib), HS-20117 will first be studied in combination with the standard dose of aumolertinib, to assess the efficacy, safety, tolerability, PK profile, and immunogenicity of HS-20117 in combination with aumolertinib in the target population, as well as to determine the recommended Phase III dose (RP3D). Following confirmation of the safety and efficacy of HS-20117 in combination with aumolertinib and RP3D in Phase Ib, a randomized, active-controlled, open-label, multicenter Phase III study will be initiated to assess the efficacy and safety of HS-20117 in combination with aumolertinib versus aumolertinib in the target population in the confirmatory study phase.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,080

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males or females aged 18 - 75 years (inclusive). * Participants with newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic EGFR-sensitive mutated NSCLC (stage IIIB/IIIC/IV) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation. * Agree to provide fresh or archival tumor tissue. * At least one target lesion per the RECIST v1.1. * ECOG performance status of 0-1. * Minimum life expectancy \> 12 weeks. * Males or Females should be using adequate contraceptive measures throughout the study. * Females must not be pregnant at screening or have evidence of non-childbearing potential. * Have signed Informed Consent Form. Exclusion Criteria: * Received or are receiving the following treatments: 1. Previous or current treatment with MET targeted therapy or EGFR targeted antibodies or antibody-drug conjugates (ADC). 2. Traditional Chinese medicine indicated for tumors, major surgery or other local therapy within washout period to the first dose of study drug. 3. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion. 4. Other investigational non-anti-tumor drugs, strong CYP3A4 inhibitors, strong inducers, drugs that are sensitive substrates of BCRP or P-gp, or drugs that prolong the QT interval within the washout period. * Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy. * History of other primary malignancies. * Untreated, or active central nervous system metastases. * Inadequate bone marrow reserve or organ functions. * Severe, uncontrolled or active cardiovascular disorders. * Severe or uncontrolled systemic diseases. * Severe bleeding symptoms or bleeding tendencies. * Severe arteriovenous thrombosis occurred. * Serious or active infection. * Active infectious diseases. * Interstitial lung disease (ILD). * Serious neurological or mental disorders. * History of hypersensitivity to any component of HS-20117 and Aumolertinib or their similar drugs. * Female subjects who are pregnant, lactating, or planning to become pregnant or breastfeed during the study period or within 6 months after the last dose of the study drug. * Subjects with a history of severe allergic reactions or those who have experienced severe infusion reactions * Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.

Outcomes

Primary Outcomes

[Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)

ORR is defined as the percentage of participants with DOR 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, up to approximately 40 months

[Phase III] Progression-Free Survival (PFS) According to RECIST v1.1 by Independent Review Committee(IRC)

PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on IRC using RECIST v1.1

Time frame: Up to approximately 40 months

Secondary Outcomes

[Phase Ib and III] Overall Survival (OS)

Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.

Time frame: Approximately 60 months

[Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs

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) based on Investigator's assessment per RECIST v1.1.

Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.

[Phase Ib and III] Duration of response (DoR) According to RECIST v1.1 by INVs

DoR only applies to participants whose best overall response is CR or PR based on Investigator's 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 40 months.

[Phase Ib and III] Progression-Free Survival (PFS) According to RECIST v1.1 by INVs

PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on IRC using RECIST v1.1

Time frame: Up to approximately 40 months

[Phase III] ORR According to RECIST v1.1 by INVs

ORR is defined as the percentage of participants with BOR of CR or PR per RECIST v1.1

Time frame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months

[Phase III] ORR According to RECIST v1.1 by IRC

ORR is defined as the percentage of participants with BOR of CR or PR per RECIST v1.1

Time frame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months

[Phase III] DCR According to RECIST v1.1 by IRC

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)

Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.

[Phase III] DoR According to RECIST v1.1 by IRC

DoR only applies to participants whose best overall response is CR or PR. 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 40 months.

[Phase Ib and III] 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 Ib and III] 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).

[Phase Ib] 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 Ib] PK parameters: Trough serum concentration (Ctrough) of HS-20117

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 Ib] 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 Ib] 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 Ib] 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.

A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts