Pucotenlimab Combined with MRG002 for HER2-positive Cancer of Unknown Primary

A Phase II Clinical Trial to Evaluate the Efficacy and Safety of Pucotenlimab in Combination with MRG002 in Treating HER2-positive Cancer of Unknown Primary

This study is a single-arm, open-label, multicenter Phase II clinical trial designed to observe and evaluate the efficacy and safety of Pucotenlimab in combination with MRG002 in patients with HER2-positive (IHC 2+ or 3+) cancer of unknown primary.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer of Unknown Primary
• Intervention / Treatment: Drug: Pucotenlimab combined with MRG002

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiguo Luo, MD; Phone Number: (+86)-021-64175590; Email: luozhiguo88@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Zhiguo Luo, MD; Phone Number: (+86)-021-64175590; Email: luozhiguo88@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements.
2. Subjects must be ≥18 years of age on the day of signing the informed consent form, with no gender restrictions.
3. Expected survival of ≥3 months.
4. Subjects with histologically confirmed squamous cell carcinoma, adenocarcinoma, or undifferentiated carcinoma of unknown primary origin by pathology laboratory, and who also meet the criteria of HER2 immunohistochemistry (IHC) 2+ or 3+. Subjects must have received at least one line of systemic therapy, including but not limited to targeted therapy, immunotherapy, chemotherapy, etc.
5. Subjects must be able to provide a tumor specimen for pathological testing (paraffin block, paraffin-embedded sections, or fresh tissue sections are acceptable).
6. Radiological evidence of disease progression during or after the most recent treatment, as confirmed by the investigator; according to RECIST 1.1 criteria, at least one measurable lesion at baseline.
7. Adverse events (AEs) related to prior anti-tumor therapy must have resolved to ≤Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), with the exception of alopecia, non-clinically significant or asymptomatic laboratory abnormalities.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to dosing.
9. No severe cardiac dysfunction, with a left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to dosing.
10. Adequate organ function.
11. Agree to contraception from the time of signing the informed consent form until 6 months after the last dose of the investigational drug. Women of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose of the investigational drug.

Exclusion Criteria:

1. History of other primary malignancies.
2. Received prohibited treatments as per the protocol.
3. Untreated or unstable brain metastases, spinal metastases or compression, carcinomatous meningitis, or leptomeningeal metastases.
4. Presence of ascites, pleural effusion, pericardial effusion that cannot be controlled by drainage methods, or subjects who require drainage to control third-space effusions within 14 days before dosing.
5. Any severe or uncontrolled systemic disease, as judged by the investigator, including poorly controlled hypertension, uncontrolled diabetes, or signs of active bleeding.
6. History of uncontrolled cardiac disease, including heart failure greater than NYHA Class II, unstable angina, myocardial infarction within the past year, clinically significant supraventricular or ventricular arrhythmias requiring treatment, or prolonged QT syndrome.
7. Evidence of active infection, including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection; uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections, unless treated and resolved before administration of the investigational drug.
8. History of allergy to Pucotenlimab or any component of MRG002, or history of ≥Grade 3 allergic reaction to macromolecular protein preparations/monoclonal antibodies.
9. History of primary immunodeficiency or active autoimmune disease, current use of immunosuppressive agents, or systemic corticosteroid therapy (≥10 mg/day prednisone or equivalent), and continued use within 2 weeks before enrollment.
10. History of or concurrent interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
11. Positive serum pregnancy test or breastfeeding women who do not agree to adequate contraception during the study and for 6 months after receiving the investigational drug.
12. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm	Drug: Pucotenlimab combined with MRG002; Pucotenlimab 200mg iv d1, Q3W MRG002 2.2mg/kg d1, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response and was assessed using RECIST 1.1 based on investigator evaluation.	Time from the date of recruiting to the first recorded complete remission (CR) or partial remission (PR), assessed up to 12 months.

Collaborators and Investigators

• Sponsor: Zhiguo Luo, MD, PhD

Study record dates

Study Major Dates

• Study Start (Estimated): March 8, 2025
• Primary Completion (Estimated): March 8, 2027
• Study Completion (Estimated): August 8, 2028

Study Registration Dates

• First Submitted: March 5, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CUP 004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No