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

Phase 1

Active, not recruiting

• Conditions: Locally Advanced or Metastatic Solid Tumors; Squamous-cell Non-small Cell Lung Cancer
• Interventions: Drug: HLX35

• Registration Number: NCT05360381
• Lead Sponsor: Shanghai Henlius Biotech

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-04-29
• Study First Posted: 2022-05-04
• Study Start: 2022-06-03
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-07
• Last Update Posted: 2023-08-08
• Primary Completion: 2024-10-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 82

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1a dose-escalation stage	HLX35	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
Phase 1b dose-expansion stage	HLX35	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Peak plasma concentration (Cmax) 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
Time to peak (Tmax) of HLX35	2 years
Area under the concentration-time curve (AUC) of HLX35	2 years
The level of 4-1BB in serum	2 years
Duration of response (DOR)	2 years
Incidence of treatment-emergent anti-drug antibodies (ADA)	2 years
Objective response rate (ORR)	2 years
Disease control rate (DCR)	2 years

Trial Locations

Locations (2)

THE Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China