A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations
- Conditions
- Advanced Solid Tumors With HER2
- Registration Number
- jRCT2031210132
- Lead Sponsor
- Daiichi Sankyo Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 100
- Adults >=18 years old. Other age restrictions may apply as per local regulations.
- Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772_A775dup / A775_G776insYVMA, L755S, G778_P780dup / P780_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) ) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
- Prior HER2 targeted therapy is permitted.
- All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
- LVEF >=50%
- ECOG 0-1
- All patients have measurable target disease assessed by the Investigator based on RECIST v1.1
- HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
- HER2 mutant NSCLC.
- Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke.
- History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening.
- Corrected QT interval by Fridericia's formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG.
- Lung-specific intercurrent clinically significant severe illnesses.
- History of active primary immunodeficiency, known HIV, active HBV or HCV infection.
- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
- Has spinal cord compression or clinically active central nervous system metastases.
Study & Design
- Study Type
- Interventional
- Study Design
- single assignment
- Primary Outcome Measures
Name Time Method Confirmed objective response rate by RECIST 1.1 based on independent central review (ICR) An average of approximately 12 months. Confirmed ORR per RECIST 1.1 is the proportion of patients with Complete Response or Partial Response that is subsequently confirmed, based on ICR.
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) based on ICR and Investigator assessment An average of approximately 12 months. PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on ICR and Investigator assessment.
Proportion of patients alive and progression-free At 6 and 12 months. Proportion of patients who are alive and progression-free based on ICR and Investigator assessment.
Confirmed Objective Response Rate (ORR) based on investigator assessment An average of approximately 12 months. Confirmed ORR per RECIST 1.1 is the proportion of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
Overall survival (OS) An average of approximately 20 months. OS is the time form the date of first dose of study treatment until death due to any cause.
Occurrence of adverse events (AEs) and serious adverse events (SAEs) An average of approximately 14 months. Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Serum concentration of T-DXd An average of approximately 14 months. Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
Serum concentration of total anti-HER2 antibody An average of approximately 14 months. Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
Serum concentration of MAAA-1181a An average of approximately 14 months. Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for MAAA-1181a.
The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd An avarage of approximately 14 months. Individual participant data and descriptive statistics will be provided for data at each time point.
Duration of response (DoR) based on ICR and Investigator assessment 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 or death, based on ICR and Investigator assessment.
Disease control rate (DCR) based on ICR and Investigator assessment An average of approximately 12 months. DCR is the proportion of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on ICR and Investigator assessment.