Clinical trial NCT06417008: A Study of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer
Official title: A Phase Ib/III Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Immunogenicity of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
HS-20117
Epidermal Growth Factor Receptor
c-Mesenchymal-Epithelial Transition
Bispecific Antibody
Lead sponsor: Hansoh BioMedical R&D Company
Sponsor class: INDUSTRY
First posted: 2024-05-16
Enrollment: 1080
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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 within 2 weeks prior to the first dose of study drug.
  3. Local radiotherapy within 2 weeks prior to the first dose of study drug, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of study drug.
  4. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
  5. Major surgery within 4 weeks prior to the first dose of study drug.
* 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 within 1 month prior to the first dose of study drug.
* Severe arteriovenous thrombosis occurred within 3 months prior to the first dose of study drug.
* Serious infection within 4 weeks prior to the first dose of study drug.
* 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.
* Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.

Primary outcomes:
measure: [Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
measure: [Phase III] Progression-Free Survival (PFS) According to RECIST v1.1 by Independent Review Committee(IRC)
timeFrame: Up to approximately 40 months
Secondary outcomes:
measure: [Phase Ib and III] Overall Survival (OS)
timeFrame: Approximately 60 months
measure: [Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.
measure: [Phase Ib and III] Duration of response (DoR) According to RECIST v1.1 by INVs
timeFrame: From the date of CR, PR until the date of disease progression or death, approximately 40 months.
measure: [Phase Ib and III] Progression-Free Survival (PFS) According to RECIST v1.1 by INVs
timeFrame: Up to approximately 40 months
measure: [Phase III] ORR According to RECIST v1.1 by INVs
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
measure: [Phase III] ORR According to RECIST v1.1 by IRC
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
measure: [Phase III] DCR According to RECIST v1.1 by IRC
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.
measure: [Phase III] DoR According to RECIST v1.1 by IRC
timeFrame: From the date of CR, PR until the date of disease progression or death, approximately 40 months.
measure: [Phase Ib and III] Incidence and severity of treatment-emergent adverse events
timeFrame: From the date of first dose until 90 days after the final dose. A cycle is 28 days.
measure: [Phase Ib and III] Immunogenicity of HS-20117
timeFrame: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).
measure: [Phase Ib] PK parameters: Maximum serum concentration (Cmax) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [Phase Ib] PK parameters: Trough serum concentration (Ctrough) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [Phase Ib] PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days
measure: [Phase Ib] PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
measure: [Phase Ib] PK parameters: Terminal elimination half-life (t1/2) of HS-20117
timeFrame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
Other outcomes:
Locations:
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Dingzhi Huang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Cancer Hspital
name: Yun Fan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: