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

May 16, 2024 updated by: Hansoh BioMedical R&D Company

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

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1080

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ib: HS-20117 and Aumolertinib
Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
Drug: HS-20117
Participants will receive HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)
Other Names:
  • PM1080
Drug: Aumolertinib
110 mg orally once daily.
Other Names:
  • HS-10296
  • Almonertinib
  • Almonertinib Mesilate Tablets
Experimental: Phase III: HS-20117 and Aumolertinib
Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
Drug: HS-20117
Participants will receive HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)
Other Names:
  • PM1080
Drug: Aumolertinib
110 mg orally once daily.
Other Names:
  • HS-10296
  • Almonertinib
  • Almonertinib Mesilate Tablets
Active Comparator: Phase III: Aumolertinib
Participants will receive Aumolertinib 110 mg orally once daily.
Drug: Aumolertinib
110 mg orally once daily.
Other Names:
  • HS-10296
  • Almonertinib
  • Almonertinib Mesilate Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
[Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)
Time Frame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
ORR is defined as the percentage of participants with DOR of confirmed CR or confirmed PR per RECIST v1.1
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)
Time Frame: Up to approximately 40 months
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
Up to approximately 40 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
[Phase Ib and III] Overall Survival (OS)
Time Frame: Approximately 60 months
Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
Approximately 60 months
[Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs
Time Frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.
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.
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
Time Frame: From the date of CR, PR until the date of disease progression or death, approximately 40 months.
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.
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
Time Frame: Up to approximately 40 months
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
Up to approximately 40 months
[Phase III] ORR According to RECIST v1.1 by INVs
Time Frame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1
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
Time Frame: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1
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
Time Frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.
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)
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
Time Frame: From the date of CR, PR until the date of disease progression or death, approximately 40 months.
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.
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
Time Frame: From the date of first dose until 90 days after the final dose. A cycle is 28 days.
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.
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
Time Frame: Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).
Immunogenicity will be measured by the number of participants that are ADA positive.
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
Time Frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
The Cmax is the maximum observed serum concentration of HS-20117
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
Time Frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
Ctrough is the observed serum concentration immediately prior to the next administration
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
Time Frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days
The AUCtau is defined as the area under the serum concentration-time curve during a dose interval time period(tau)
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
Time Frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
The Tmax is defined as time to reach maximum observed serum concentration of HS-20117
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
Time Frame: From the date of first dose until 30 days after the final dose. A cycle is 28 days.
The t1/2 is defined as the time it takes for the concentration levels to fall to 50% of their value.
From the date of first dose until 30 days after the final dose. A cycle is 28 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hansoh BioMedical R&D Company

Investigators

  • Principal Investigator: Dingzhi Huang, M.D., Tianjin Medical University Cancer Institute and Hospital
  • Principal Investigator: Yun Fan, M.D., Zhejiang Cancer Hspital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

May 12, 2024

First Submitted That Met QC Criteria

May 12, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 20, 2024

Last Update Submitted That Met QC Criteria

May 16, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-20117-301

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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