Trastuzumab Rezetecan in Advanced Solid Tumors Refractory to Standard Therapies

NCT07309770 | Recruiting Phase 2

• 1 other identifier: A1811-US-03
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, multi-cohort, phase II clinical trial. Eligible patients with HER2-positive advanced solid tumors were enrolled after providing informed consent. A total of 90 patients were allocated into three cohorts (30 patients each): those with Extramammary Paget's Disease (EMPD), rare solid tumors, or urothelial carcinoma, who had experienced failure of standard treatment or for whom no standard treatment was available. The participant recruitment period was 12 months, and the follow-up duration was 12 months. All patients received Trastuzumab Rezetecan (SHR-A1811) at a dose of 4.8 mg/kg administered every three weeks (q3w). They were followed until disease progression, withdrawal from the study, loss to follow-up, or death, whichever occurred first. Tumor response was assessed radiologically every 6 weeks during treatment. Safety follow-up was conducted 30 days after the last dose, followed by survival follow-up every 3 months thereafter.

Conditions

Urachal Cancer; Advanced Solid Tumor Cancer; Antibody-drug Conjugates

Keywords

Antibody-Drug Conjugates; Rare tumor; Extra-mammary Paget disease; Urachal cancer; Trastuzumab Rezetecan

Outcome Measures

Primary Outcomes (1)

• The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.

  Objective Response Rate (ORR)

  Efficacy was assessed every 9 weeks for 1 year and every 12 weeks thereafter (assessed up to 3 years).

Secondary Outcomes (3)

• Time from treatment start to progression by RECIST V.1.1.

  From date of treatment until the date of first documented progression, assessed up to 100 months.

• Time from treatment start to death of participants.

  From date of treatment until the date of death from any cause, whichever came first, assessed up to 100 months.

• Type, incidence, severity, onset and end time of adverse events (AE) evaluated according by the version 5.0 of NCI-CTCAE.

  Began at 30 days (±7 days) after the last study treatment to 1 year.

Study Arms (1)

Experimental group 1

EXPERIMENTAL

Cohort1:Patients with histologically confirmed extramammary Paget's disease (EMPD) demonstrating HER2 expression (IHC ≥ 1+) and having unresectable locally advanced or metastatic disease. Cohort2: Patients with histologically confirmed locally advanced or metastatic rare solid tumors (such as sarcoma, urachal carcinoma, etc.) demonstrating HER2 expression (IHC ≥ 1+) , who have experienced disease progression on or after standard therapy, or for whom no standard therapy is available, and with at least one measurable lesion. Cohort3:Patients with histologically confirmed locally advanced or metastatic urothelial carcinoma demonstrating HER2 expression (IHC ≥ 1+) , who have experienced disease progression following first-line treatment with a PD-1/PD-L1 inhibitor in combination with Enfortumab Vedotin or Disitamab vedotin

Drug: SHR-A1811; Drug: Trastuzumab Rezetecan

Interventions

SHR-A1811 DRUG

Trastuzumab Rezetecan (SHR-A1811) is administered at a dose of 4.8 mg/kg every 21 days (q3w), constituting one treatment cycle.

Experimental group 1

Trastuzumab Rezetecan DRUG

Patients who have failed standard therapy are treated with Trastuzumab Rezetecan

Experimental group 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign a written informed consent form.
• Age ≥ 18 years.
• Diagnosed with the corresponding advanced tumor confirmed by histology and/or cytology, combined with imaging or ultrasound assessment, and pathologically confirmed as HER2-positive (i.e., HER2 ≥ 1+ by immunohistochemistry \[IHC\]).
• Cohort 1 only: Histologically confirmed extramammary Paget's disease (EMPD) with unresectable locally advanced or metastatic disease.
• Cohort 2 only: Histologically confirmed locally advanced or metastatic rare solid tumor (e.g., sarcoma, urachal cancer) refractory to standard treatment or for whom no standard treatment is available.
• Cohort 3 only: Histologically confirmed locally advanced or metastatic urothelial carcinoma with disease progression following first-line treatment with a PD-1/PD-L1 inhibitor combined with enfortumab vedotin or disitamab vedotin.
• ECOG Performance Status: 0 to 2.
• At least one measurable lesion (according to RECIST v1.1 criteria: non-nodal lesions with longest diameter ≥10 mm on CT scan, nodal lesions with short axis ≥15 mm on CT scan).
• Hematological function:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count (PLT) ≥ 70 × 10⁹/L
• Hemoglobin (HGB) ≥ 80 g/L
• Hepatic function:
• Serum total bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN)
• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if liver metastases are present)

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation in this study:
• Presence of any severe and/or uncontrolled disease, including:
• Poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); poorly controlled diabetes (fasting blood glucose \[FBG\] \> 10 mmol/L).
• ≥ Grade 2 myocardial ischemia, myocardial infarction, arrhythmia (QTcF ≥ 470 ms), or ≥ Grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification).
• Active or uncontrolled severe infection (≥ CTCAE Grade 2 infection) requiring systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis infection.
• History of active tuberculosis.
• Uncontrolled ascites, pericardial effusion, or pleural effusion requiring repeated drainage.
• History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known presence of brain metastases, leptomeningeal metastasis, spinal cord compression, or spinal metastasis.
• Within 6 months prior to the first dose: history of esophageal/gastric varices, severe ulcer, unhealed wound, gastrointestinal perforation, abdominal fistula, intestinal obstruction, intra-abdominal abscess, acute gastrointestinal bleeding; extensive intestinal resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
• Presence of non-healing or poorly healed wounds, active ulcers.
• Toxicity from previous antineoplastic therapy that has not resolved to ≤ Grade 1 per NCI CTCAE v5.0 (except for alopecia).
• Major surgical treatment, open biopsy, or significant traumatic injury within 28 days prior to the start of study treatment; or presence of long-term unhealed wounds or fractures.
• History of severe hypersensitivity reaction to monoclonal antibodies; known allergy to the active components or excipients of the study drug(s).

Sponsors & Collaborators

• Sheng Zhang: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Urachal cancer; Paget Disease, Extramammary

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary

Central Study Contacts

Sheng Zhang

CONTACT

+86 021-64175590; wozhangsheng@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Model Details: single-group study,three cohorts

Study Record Dates

• First Submitted: September 28, 2025
• First Posted: December 30, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): September 11, 2027
• Study Completion (Estimated): March 11, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-09

Locations

CN (1)