HLX35(EGFR×4-1BB Bispecific) in Patients With Advanced or Metastatic Solid Tumors

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Initial Efficacy of HLX35 (Recombinant Human Anti-EGFR and Anti-4-1BB Bispecific Antibody) in Patients With Advanced or Metastatic Solid Tumors

This Phase1, multicenter, first-in-human, open-label, dose-escalation, and dose expansion study will evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy of HLX35 administered as a single-agent by IV infusion every 2 weeks to patients with locally advanced or metastatic solid malignancies, who have failed or are intolerant to standard therapy, or for whom no standard therapy is available. This study has two parts: phase 1a dose escalation and phase 1b dose expansion.

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors; Squamous-cell Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: HLX35

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200000
    • Fudan University Shanghai Cancer Center
  • Xuzhou, China
    • The Affiliated Hospital of Xuzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Volunteer to participate in this clinical study; completely understand and know this study as well as sign the informed consent form (ICF);
• Age ≥ 18 years;
• Phase 1a dose escalation: patients must have histologically or cytologically confirmed malignant solid tumors which are advanced or metastatic, have failed prior standard treatment, and be intolerant or ineligible for standard therapy;
• Phase 1b dose expansion: patients must have a histological or cytological diagnosis of Squamous Non-Small Cell Lung Cancer (EGFR H score ≥200 confirmed by central lab) which is advanced or metastatic, have failed prior standard treatment, and be intolerant or ineligible for standard therapy;
• Measurable disease according to RECIST Version 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Expected survival 12 weeks;
• Adequate organ function;

Exclusion Criteria:

• Systemic anti-cancer treatment or investigational agents in the 28 days prior to the first study dosing;
• Patients who still have persistent ≥ grade 2 toxicities from prior therapies;
• Active CNS metastasis;
• History of any secondary malignancy in the past 5 years;
• Active autoimmune disease;
• Human immunodeficiency virus (HIV) infection;

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a dose-escalation stage; Phase 1a uses the "3+3" design, to investigate the safety and determine the MTD of HLX35. Seven dose levels of 0.015 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg are planned for dose finding. Enrollment will continue until a maximum of 42 patients are enrolled	Drug: HLX35; A Recombinant Human Anti-EGFR and Anti-4-1BB Bispecific Antibody, HLX35 will be administered as a single intravenous (IV) infusion on Day 1 in each 14-day cycle
Experimental: Phase 1b dose-expansion stage; Patients with sqNSCLC (EGFR H score≥200) will be enrolled in two expansion cohorts, at doses equal to or lower than the MTD, to better characterize the safety, tolerability, PK variability, and preliminary efficacy of single-agent HLX35. Phase 1b dose expansion will include 15-20 per-protocol treated patients, as defined above, in each of the two expansion cohorts.	Drug: HLX35; A Recombinant Human Anti-EGFR and Anti-4-1BB Bispecific Antibody, HLX35 will be administered as a single intravenous (IV) infusion on Day 1 in each 14-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Related Adverse Events	2 years
The proportion of patients experiencing dose limiting toxicity (DLT) events	from first dose to the end of Cycle 2 (each cycle is 14 days)
The maximum tolerated dose (MTD)	from first dose to the end of Cycle 2 (each cycle is 14 days)
Recommended phase 2 dose (RP2D)	from first dose to the end of Cycle 2 (each cycle is 14 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response (DOR)	2 years
Objective response rate (ORR)	2 years
Peak plasma concentration (Cmax) of HLX35	2 years
Time to peak (Tmax) of HLX35	2 years
Area under the concentration-time curve (AUC) of HLX35	2 years
Elimination half-life (t1/2) of HLX35	2 years
Clearance (CL) of HLX35	2 years
Volume of distribution (Vz) of HLX35	2 years
Accumulation Index (Rac) of HLX35	2 years
4-1BB receptor occupancy on circulating T cells	2 years
The level of 4-1BB in serum	2 years
Incidence of treatment-emergent anti-drug antibodies (ADA)	2 years
Disease control rate (DCR)	2 years

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2022
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HLX35-FIH101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No