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

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06417008
• Other study ID #: HS-20117-301
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: June 1, 2024
• Est. completion date: June 1, 2030

Study information

• Verified date: May 2024
• Source: Hansoh BioMedical R&D Company
• Contact: Jialei Fu
• Phone: +86 18652105685
• Email: fujl[@]hspharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1080
• Est. completion date: June 1, 2030
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Squamous Non-Small Cell Lung Cancer

Intervention

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)
• Aumolertinib
110 mg orally once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hansoh BioMedical R&D Company

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[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	From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
Primary	[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	Up to approximately 40 months
Secondary	[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.	Approximately 60 months
Secondary	[Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs	DCR is de?ned 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.
Secondary	[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.	From the date of CR, PR until the date of disease progression or death, approximately 40 months.
Secondary	[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	Up to approximately 40 months
Secondary	[Phase III] ORR According to RECIST v1.1 by INVs	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
Secondary	[Phase III] ORR According to RECIST v1.1 by IRC	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
Secondary	[Phase III] DCR According to RECIST v1.1 by IRC	DCR is de?ned 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.
Secondary	[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.	From the date of CR, PR until the date of disease progression or death, approximately 40 months.
Secondary	[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.	From the date of first dose until 90 days after the final dose. A cycle is 28 days.
Secondary	[Phase Ib and III] Immunogenicity of HS-20117	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).
Secondary	[Phase Ib] PK parameters: Maximum serum concentration (Cmax) of HS-20117	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.
Secondary	[Phase Ib] PK parameters: Trough serum concentration (Ctrough) of HS-20117	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.
Secondary	[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)	From the date of first dose until 30 days after the final dose. A cycle is 28 days
Secondary	[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	From the date of first dose until 30 days after the final dose. A cycle is 28 days.
Secondary	[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.	From the date of first dose until 30 days after the final dose. A cycle is 28 days.