A Phase I Multicentre Randomized Double-Blind Parallel-Controlled Study of HLX05-N vs. ERBITUX® in Metastatic Colorectal Cancer (PK similarity)

A Multicentre, Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Study to Evaluate the Pharmacokinetic, Efficacy, Safety, and Immunogenicity Profiles of HLX05-N vs. ERBITUX® (US/EU-sourced) in Participants With Metastatic Colorectal Cancer

This is a multicentre, randomized, double-blind, parallel-controlled Phase 1 clinical study designed to evaluate the pharmacokinetic (PK) similarity, efficacy, safety, and immunogenicity of HLX05-N compared with US-sourced ERBITUX® and EU-sourced ERBITUX® in participants with metastatic colorectal cancer (mCRC) with wild-type KRAS/NRAS and no BRAF V600E mutation.

Approximately 387 participants will be randomized in a 1:1:1 ratio to receive HLX05-N, US-ERBITUX®, or EU-ERBITUX®. Randomization will be stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1) and sex (male vs. female).

During the treatment period, participants will receive study treatment in combination with mFOLFOX6 chemotherapy. For the first 3 treatment cycles, participants will receive HLX05-N or US-/EU-ERBITUX® plus chemotherapy according to randomized assignment. After completion of the initial 3 cycles, participants originally assigned to the US-ERBITUX® or EU-ERBITUX® arms will switch, in a blinded manner, to HLX05-N 250 mg/m² administered in combination with chemotherapy on Day 1 of each cycle. Study treatment will continue until investigator-assessed disease progression, death, initiation of new anti-tumor therapy, unacceptable toxicity, withdrawal of informed consent, study termination, or 1 year after randomization, whichever occurs first.

For participants with disease response or stable disease after 12 cycles of treatment, oxaliplatin may be discontinued, and maintenance therapy with cetuximab in combination with leucovorin and 5-fluorouracil may continue. Participants who continue to benefit from treatment after 1 year following randomization may receive subsequent therapy according to local clinical practice.

PK and anti-drug antibody (ADA) samples will be collected from all participants to assess PK characteristics and immunogenicity. An end-of-treatment visit will be performed within 7 days after treatment discontinuation. Safety follow-up will be conducted 30 days after the last dose, with an additional telephone safety follow-up at 12 weeks after the last dose. Survival follow-up will continue for up to 1 year after randomization.

Study Overview

• Status: Not yet recruiting
• Conditions: mCRC
• Intervention / Treatment: Drug: Cetuximab; Drug: mFOLFOX6

• Study Type: Interventional
• Enrollment (Estimated): 387
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fuyu Yang; Phone Number: 021-33395800; Email: Fuyu_Yang@Henlius.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Participants must have signed and dated an IRB/IEC approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines, and is willing to comply with all study procedures and rules required by the protocol.

  2. Male or female aged 18-75 years (inclusive) when signing the ICF. 3. 18.5 kg/m2 ≤ Body mass index (BMI) ≤ 30 kg/m2 and 50kg ≤ Body weight ≤ 85kg. 4. Participants with a KRAS and NRAS wild type and with no BRAF V600E mutation mCRC.

  5. Participants have histologically or cytologically documented locally advanced (unresectable) or metastatic colorectal adenocarcinoma originating from the splenic flexure to the rectum (left colon and rectum).

  6. Has not previously received first-line systemic anti-tumor therapy (including systemic chemotherapy, molecular targeted therapy, biological therapy, and other investigational drugs) for recurrent or metastatic CRC

Exclusion Criteria:

• 1. History of illicit drug use or alcohol abuse in the investigator's judgment within 12 months prior to screening.

  2. Prior treatment with VEGF pathway-targeted therapy, EGFR pathway-targeted therapy, or signal transduction inhibitors (e.g., tyrosine kinase inhibitors).

  3. Received radiotherapy within 6 months prior to randomization, with the exception of palliative radiotherapy for bone lesions completed more than 14 days prior to randomization. Radiotherapy covering more than 30% of the bone marrow area within 28 days prior to randomization is not permitted.

  4. Underwent any major surgery within 4 weeks prior to randomization, or has not fully recovered from any surgery (placement of a vascular access device is not considered a major or minor surgery). For this study, a major surgery is defined as a procedure requiring at least a 3-week recovery period before the participant can receive treatment under this protocol.

  5. Has had other active malignancies within 5 years prior to randomization. Participants with cured localized tumors, such as basal cell carcinoma in situ of the skin, squamous cell carcinoma in situ of the skin, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, breast carcinoma in situ, or thyroid carcinoma in situ, may be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; HLX05-N	Drug: Cetuximab; 400 mg/m2 administered as about 120-minute intravenous infusion on the first day of treatment. If the first infusion is well tolerated, then 250 mg/m2 intravenous infusion in about 1 hour weekly; Drug: mFOLFOX6; Oxaliplatin, Leucovorin, 5-FU
Active Comparator: US-sourced Erbitux®; US-ERBITUX®	Drug: Cetuximab; 400 mg/m2 administered as about 120-minute intravenous infusion on the first day of treatment. If the first infusion is well tolerated, then 250 mg/m2 intravenous infusion in about 1 hour weekly; Drug: mFOLFOX6; Oxaliplatin, Leucovorin, 5-FU
Active Comparator: EU-sourced Erbitux®; EU-ERBITUX®	Drug: Cetuximab; 400 mg/m2 administered as about 120-minute intravenous infusion on the first day of treatment. If the first infusion is well tolerated, then 250 mg/m2 intravenous infusion in about 1 hour weekly; Drug: mFOLFOX6; Oxaliplatin, Leucovorin, 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• Area under the serum concentration-time curve from time 0 to 7 days (AUC0-7d) after the 1st dose	day 0 to day 7 after the 1st dose
Area under the serum concentration-time curve within a dosing interval at steady state (AUCss) after the 3rd dose	from 0 to 21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
maximum serum drug concentration (Cmax)	from day 0 to week 51
Objective response rate (ORR) assessed by the Investigators (based on RECIST v1.1)	from day 0 to week 51
Time to response (TTR) assessed by the Investigators (based on RECIST v1.1)	from day 0 to week 51
Adverse Events (AEs)	from day 0 to week 51
Incidence of anti-drug antibody (ADA)	from day 0 to week 51

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab
• Other Study ID Numbers: HLX05-N-mCRC102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data underlying the results reported in this study, the study protocol, and statistical analysis plan may be made available.
• IPD Sharing Time Frame: Data may be available beginning 6 months after publication of the primary results and ending 5 years after publication.
• IPD Sharing Access Criteria: Access may be provided to qualified researchers who submit a methodologically sound research proposal, subject to review and approval by the sponsor.

Drug and device information, study documents

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