Locally Advanced or Metastatic Solid Tumors, Squamous-cell Non-small Cell Lung Cancer
Conditions
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.
Interventions
DRUGHLX35
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
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
| The proportion of patients experiencing dose limiting toxicity (DLT) events | from first dose to the end of Cycle 2 (each cycle is 14 days) |
| Incidence of Treatment-Related Adverse Events | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Peak plasma concentration (Cmax) of HLX35 | 2 years |
| Incidence of treatment-emergent anti-drug antibodies (ADA) | 2 years |
| Objective response rate (ORR) | 2 years |
| Disease control rate (DCR) | 2 years |
| Duration of response (DOR) | 2 years |
| The level of 4-1BB in serum | 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 |
Countries
China
Outcome results
None listed