Phase Ib Trial of HS-20117 in Combination With Other Drugs in Advanced Solid Tumors (HS-20117)

Safety, Tolerability, Efficacy, Pharmacokinetics Profile and Immunogenicity of HS-20117 in Combination With Other Drugs in Advanced Solid Tumors, a Phase Ib Clinical Trial

HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity of HS-20117 in combination with other drugs in advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer; Solid Tumors
• Intervention / Treatment: Drug: HS-20117 combined Platinum-containing chemotherapy; Drug: HS-20117 combined HS-20093; Drug: HS-20117 combined HS-20093 and 5-FU; Drug: HS-20117+CAPEOX; Drug: HS-20117+FOLFIRI; Drug: HS-20117+mFOLFOX6

Detailed Description

This is a multicenter, open-label, Phase Ib clinical trial of HS-20117 combination therapies to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity in participants with advanced solid tumors. The study includes a dose escalation part and a dose expansion part. The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 combination therapies in participants with advanced solid tumor. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 combination therapies in participants with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations or EGFR classical mutations, and RAS/BRAF V600E wild type CRC.

• Study Type: Interventional
• Enrollment (Estimated): 780
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaowei Yan; Phone Number: 13061877102; Email: yanxw@hspharm.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute & Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females aged 18 - 75 years (inclusive).
• Histologically confirmed unresectable, recurrent or metastatic solid tumors.
• 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.
• Signed Informed Consent Form.

Exclusion Criteria:

• Received or are receiving the following treatments:

  1. Any anticancer therapy targeting MET, including TKIs, antibodies or antibody-drug conjugates.
  2. Monoclonalor bispecific antibodies targeting EGFR.
  3. Systemic anti-cancer treatment (Cytotoxicities and anti-cancer Traditional Chinese medicine or TKIs) within 2 weeks prior to the first dose of HS-20117.
  4. Investigational anti-cancer drugs or antibodies or ADCs within 4 weeks prior to the first dose of HS-20117.
  5. Local radiotherapy within 2 weeks prior to the first dose of HS-20117, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of HS-20117.
  6. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
  7. Major surgery within 4 weeks prior to the first dose of HS-20117.
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• Presence of uncured secondary primary malignancies.
• Untreated, or active central nervous system metastases.
• Severe, uncontrolled or active cardiovascular disorders.
• Serious infection within 4 weeks prior to the first dose of HS-20117.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a; NSCLC	Drug: HS-20117 combined Platinum-containing chemotherapy; HS-20117 + cisplatin/carboplatin + pemetrexed
Experimental: Cohort 2a; NSCLC	Drug: HS-20117 combined HS-20093; HS-20117 + HS-20093
Experimental: Cohort 3a; CRC	Drug: HS-20117+CAPEOX; CAPOEX: Oxaliplatin+Capecitabine
Experimental: Cohort 4a; CRC	Drug: HS-20117+FOLFIRI; FOLFIRI=Irinotecan+Leucovorin Calcium+5-FU
Experimental: Cohort 5a; CRC	Drug: HS-20117+mFOLFOX6; mFOLFOX6=Oxaliplatin+Leucovorin Calcium+5-FU
Experimental: Cohort 6a; CRC	Drug: HS-20117 combined HS-20093 and 5-FU; HS-20117 + HS-20093 + 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	rom the date of first dose to 90 days after the final dose.
Tolerability of HS-20117 combination therapy: incidence of DLT events, maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-20117 in combination therapies.	MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT. 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.	From the date of first dose to day 21.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
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.	From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
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.	From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
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.	From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
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.	From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years
PK parameters: Trough serum concentration (Ctrough) of HS-20117 and HS-20093	Ctrough is the observed serum concentration immediately prior to the next administration.	From the date of first dose to 90 days after the final dose.
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 to 90 days after the final dose.
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 to 90 days after the final dose.
PK parameters: Maximum serum concentration (Cmax) of HS-20117 and HS-20093.	The Cmax is the maximum observed serum concentration of HS-20117, HS-20093.	From the date of first dose to 90 days after the final dose.
Immunogenicity of HS-20117	Immunogenicity will be measured by the number of participants that are ADA positive.	From the date of first dose to 90 days after the final dose.

Collaborators and Investigators

• Sponsor: Hansoh BioMedical R&D Company

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2024
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 29, 2024
• First Submitted That Met QC Criteria: September 29, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; Solid tumor; EGFR/c-MET bispecific antibody; B7H3 ADC
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HS-20117-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No