A Study of T-DXd as Monotherapy or in Combination With Anti-cancer Agents in Patients With Selected HER2-expressing Tumors
- Conditions
- Advanced Solid Tumors (Excluding Gastric Cancer and Breast Cancer)
- Interventions
- Registration Number
- NCT06271837
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is an open-label, multicenter, Phase II study to evaluate the efficacy and safety of trastuzumab deruxtecan as monotherapy or in combination with anti-cancer agents for the treatment in locally advanced, unresectable, or metastatic patients with selected HER2-expressing solid tumors which are not eligible for curative therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 175
- At least 18 years of age.
- Locally advanced, unresectable, or metastatic solid tumors based on most recent imaging.
- HER2 expression.
- ECOG performance status of 0-1.
- Must provide an adequate FFPE tumor sample to centrally determine HER2 status and other correlatives.
- Has measurable target disease assessed by the investigator based on RECIST 1.1.
- Adequate organ function and bone marrow within 14 days before enrollment.
- Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent.
- Provision of signed and dated written ICF prior to mandatory study-specific procedures, sampling, or analyses.
- Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner.
- Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the gastric body or gastroesophageal junction.
- Has substance abuse or any other medical conditions that may interfere with the patient's participation in the clinical study or evaluation of the clinical study results.
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and concentrated ascites reinfusion therapy.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
- Has unresolved toxicities from previous anti cancer therapy.
- Has any spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
- Uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals, or active infection including tuberculosis.
- Active primary immunodeficiency, known uncontrolled active HIV infection, or active Hepatitis B or C infection.
- Protocol-defined inadequate cardiac function.
- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Has a concomitant medical condition that would increase the risk of toxicity in the opinion of the investigator.
- Anti cancer chemotherapy without an adequate treatment washout period prior to enrollment.
- Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
- Known allergy or hypersensitivity to study treatment or any excipients of the product or other mAbs.
- Involvement in the planning and/or conduct of the study.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
- Previous enrollment in the present study. Concurrent enrollment in another therapeutic clinical study (excluding observational studies).
- For females only: Currently pregnant or breast feeding, or who are planning to become pregnant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 Cohort B Trastuzumab deruxtecan HER2 IHC 1+ gynecologic cancers Part 3 Trastuzumab deruxtecan HER2 IHC 3+ or 2+ cervical cancer Part 3 Bevacizumab HER2 IHC 3+ or 2+ cervical cancer Part 1 Trastuzumab deruxtecan HER2 IHC 3+ solid tumors (excluding breast and gastric cancer) Part 2 Cohort A Trastuzumab deruxtecan HER2 IHC 2+ solid tumors (excluding breast and gastric cancer)
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (ORR) An average of approximately 12 months Confirmed ORR is the proportion of patients who have a confirmed complete response or confirmed partial response per RECIST 1.1.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) An average of approximately 12 months PFS is defined as the time from the date of enrollment until the date of objective progressive disease (PD) per RECIST 1.1 or death.
Immunogenicity of T-DXd An average of approximately 12 months Incidence of anti-drug antibodies against T-DXd in serum at each time point.
Duration of Response (DoR) An average of approximately 12 months DoR is defined as the time from the date of first documented response until the date of documented progression (per RECIST 1.1) or death in the absence of disease progression.
Disease control rate (DCR) An average of approximately 12 months The DCR is defined as the percentage of patients who have a confirmed complete response (CR) or partial response (PR) or stable disease (SD) per RECIST 1.1.
Overall survival (OS) An average of approximately 12 months OS is defined as the time from the date of enrollment until death due to any cause.
Occurrence of adverse events (AEs) and serious adverse events (SAEs) An average of approximately 12 months The grading scales found in the revised NCI CTCAE v5.0 will be utilized for all events.
Pharmacokinetics (PK) of T-DXd An average of approximately 12 months Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a.
Confirmed best objective response (BOR) An average of approximately 12 months BOR is a patient's best response during their participation in the study up until RECIST 1.1-defined progression or the last evaluable assessment in the absence of RECIST 1.1-defined progression.
Trial Locations
- Locations (2)
Research Site
🇨🇳Zhengzhou, China
Research Site
🇨🇳Zhengzhou, China