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

NCT05360381 | Unknown Phase 1

• 1 other identifier: HLX35-FIH101
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

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.

Conditions

Locally Advanced or Metastatic Solid Tumors; Squamous-cell Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (13)

• 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

Study Arms (2)

Phase 1a dose-escalation stage

EXPERIMENTAL

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

Phase 1b dose-expansion stage

EXPERIMENTAL

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

Interventions

HLX35 DRUG

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

Phase 1a dose-escalation stage; Phase 1b dose-expansion stage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (2)

Fudan University Shanghai Cancer Center

Shanghai, 200000, China

Location

THE Affiliated Hospital of Xuzhou Medical University

Xuzhou, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 4, 2022
• Study Start: June 3, 2022
• Primary Completion: October 30, 2024
• Study Completion: December 30, 2024
• Last Updated: August 8, 2023

Record last verified: 2023-08

Locations

CN (2)