Trastuzumab Rezetecan in Advanced Solid Tumors Refractory to Standard Therapies: A Multicenter, Single-Arm, Phase II Study With Multiple Cohorts
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sheng Zhang
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
Exclusion Criteria
- •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.
- •Active hepatitis (liver enzyme levels not meeting inclusion criteria; for Hepatitis B: HBV DNA ≥ 2000 IU/ml or ≥ 10⁴ copies/ml; for Hepatitis C: HCV RNA ≥ 2000 IU/ml or ≥ 10⁴ copies/ml; carriers with chronic hepatitis B virus \[HBV DNA \< 10⁴ IU/ml\] may be enrolled if they receive concomitant antiviral therapy during the trial).
- •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.
Arms & Interventions
Experimental group 1
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
Intervention: SHR-A1811 (Drug)
Experimental group 1
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
Intervention: Trastuzumab Rezetecan (Drug)
Outcomes
Primary Outcomes
The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.
Time Frame: Efficacy was assessed every 9 weeks for 1 year and every 12 weeks thereafter (assessed up to 3 years).
Objective Response Rate (ORR)
Secondary Outcomes
- 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.)
Investigators
Sheng Zhang
Prof.
Fudan University