A Phase Ib/II Study to Evaluate HLX43 Combined With HLX07 or Serplulimab in Patients With Advanced or Metastatic Colorectal Cancer

January 14, 2026 updated by: Shanghai Henlius Biotech

A Phase Ib/II Study to Evaluate the Efficacy, Safety and Tolerance of HLX43 (an Anti-PD-L1 Antibody Conjugated) Combined With HLX07 (a Recombinant Anti-EGFR Humanized Monoclonal Antibody) or Serplulimab in Patients With Advanced or Metastatic Colorectal Cancer

This study is a phase Ib/II study to evaluate the efficacy, safety and tolerance of HLX43 combined with HLX07 or Serplulimab in patients with advanced or metastatic colorectal cancer failed or intolerance to standard first-line therapy

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a phase Ib/II study to evaluate the efficacy, safety and tolerance of HLX43 (an Anti-PD-L1 antibody conjugated) combined with HLX07 (a recombinant anti-EGFR humanized monoclonal antibody) or Serplulimab in patients with advanced or metastatic colorectal cancer failed or intolerance to standard first-line therapy In this study, eligible subjects will be randomized at 1:1 ratio in 2 different groups in 2 parts (part HLX43 + HLX07 and part HLX43 + Serplulimab) . The patients will be administered with HLX43 at different doses combined with HLX07 or Serplulimab via intravenous infusion.

Study Type

Interventional

Enrollment (Estimated)

126

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 716099
        • Sun yat-sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed advanced or metastatic colorectal adenocarcinoma; and locally tested and confirmed as a RAS/BRAF wild-type tumor (only for Part 1 );

  2. Previously failed first-line systemic anti-tumor therapy for advanced or metastatic colorectal adenocarcinoma based on a 5-FU regimen, with radiologically documented disease progression.

    Note: For patients who have previously received radical concurrent chemoradiotherapy, neoadjuvant/adjuvant chemotherapy, or chemoradiotherapy, if disease progression occurred during treatment or within ≤6 months after treatment cessation, it should be considered as first-line treatment failure; if progression occurred beyond 6 months, it should not be considered as first-line treatment failure.

  3. Patients known to have dMMR/MSI-H must have failed treatment containing a PD-1 immune checkpoint inhibitor, with radiologically documented disease progression (only for Part 1);
  4. There must be an interval of at least 4 weeks or 5 half-lives of the drug (whichever is longer) from the first dose of the investigational drug to prior major surgery, medical device treatment, local radiotherapy (except palliative radiotherapy for bone metastases), cytotoxic chemotherapy, macromolecular targeted drug therapy, immunotherapy, or biologic therapy; an interval of at least 2 weeks from prior small molecule targeted drug therapy; an interval of at least 1 week from prior traditional Chinese medicine therapy with anti-tumor indications or minor surgery; and all prior anti-tumor treatment-related adverse events (AEs) must have recovered to CTCAE v5.0 Grade ≤1 (except peripheral neuropathy and alopecia).
  5. Adequate organ function.

Exclusion Criteria:

  1. Prior exposure to any drug targeting topoisomerase I, including chemotherapy or antibody-drug conjugates (ADCs); prior treatment with anti-EGFR antibody therapy (only for Part 1); prior treatment with PD-1/PD-L1 inhibitors or any immunotherapy targeting immune checkpoints (only for Part 2).
  2. Candidates suitable for locoregional treatment with curative intent (e.g., surgery or radiotherapy).
  3. History of a second malignant neoplasm within 2 years prior to randomization, except for early-stage malignancies treated with curative intent (e.g., carcinoma in situ or Stage I tumors), such as non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, ductal carcinoma in situ of the breast, or papillary thyroid cancer.
  4. Known or suspected history of keratitis, ulcerative keratitis, or severe dry eye disease.
  5. History of adverse events leading to permanent discontinuation of prior immunotherapy; or history of ≥ Grade 2 immune-mediated pneumonitis or immune-mediated myocarditis.
  6. Use of strong inhibitors or inducers of CYP2D6 or CYP3A within 2 weeks prior to randomization.
  7. Active HBV or HCV infection or co-infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HLX43 dose 1
HLX43 dose 1 + HLX07 1000mg, Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Drug: HLX43 dose 1 + HLX07

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

HLX07 is a recombinant anti-EGFR humanized monoclonal antibody
Experimental: HLX43 dose 2
HLX43 dose 2 + HLX07 1000mg, Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Drug: HLX43 dose 2 + HLX07

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

HLX07 is a recombinant anti-EGFR humanized monoclonal antibody
Experimental: HLX43 dose 3
HLX43 dose 3 + Serplulimab 300mg, Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Drug: HLX43 dose 3 + Serplulimab

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

Serplulimab is an anti-PD-1 humanized monoclonal antibody
Experimental: HLX43 dose 4
HLX43 dose 4 + Serplulimab 300mg, Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Drug: HLX43 dose 4 + Serplulimab

HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.

Serplulimab is an anti-PD-1 humanized monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: From enrollment to 12 weeks after last patient in
Objective response rate (ORR) (assessed by BICR according to the RECIST v1.1 criteria)
From enrollment to 12 weeks after last patient in
PFS
Time Frame: rom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months
Defined as the time (in months) from randomization to the first confirmed and documented progressive disease or death (whichever occurs first) as assessed by BICR according to the RECIST v1.1 criteria.
rom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Henlius Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 31, 2026

Primary Completion (Estimated)

July 28, 2027

Study Completion (Estimated)

August 23, 2028

Study Registration Dates

First Submitted

January 14, 2026

First Submitted That Met QC Criteria

January 14, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 14, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLX43-mCRC202

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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