Clinical trial NCT05360381: HLX35(EGFR×4-1BB Bispecific) in Patients With Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Squamous-cell Non-small Cell Lung Cancer
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2022-05-04
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Incidence of Treatment-Related Adverse Events
timeFrame: 2 years
measure: The proportion of patients experiencing dose limiting toxicity (DLT) events
timeFrame: from first dose to the end of Cycle 2 (each cycle is 14 days)
measure: The maximum tolerated dose (MTD)
timeFrame: from first dose to the end of Cycle 2 (each cycle is 14 days)
measure: Recommended phase 2 dose (RP2D)
timeFrame: from first dose to the end of Cycle 2 (each cycle is 14 days)
Secondary outcomes:
measure: Peak plasma concentration (Cmax) of HLX35
timeFrame: 2 years
measure: Time to peak (Tmax) of HLX35
timeFrame: 2 years
measure: Area under the concentration-time curve (AUC) of HLX35
timeFrame: 2 years
measure: Elimination half-life (t1/2) of HLX35
timeFrame: 2 years
measure: Clearance (CL) of HLX35
timeFrame: 2 years
measure: Volume of distribution (Vz) of HLX35
timeFrame: 2 years
measure: Accumulation Index (Rac) of HLX35
timeFrame: 2 years
measure: 4-1BB receptor occupancy on circulating T cells
timeFrame: 2 years
measure: The level of 4-1BB in serum
timeFrame: 2 years
measure: Incidence of treatment-emergent anti-drug antibodies (ADA)
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Disease control rate (DCR)
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Xuzhou
country: China
facility: THE Affiliated Hospital of Xuzhou Medical University
Study officials:
References: