Treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology.
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults =18 years old. Other age restrictions may apply as per local regulations. • Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS, 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: • HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. • HER2 mutant NSCLC. • History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of T-DXd in patients with metastatic or unresectable tumors harboring specific HER2 activating mutations across tumor types.;Secondary Objective: -To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors harboring pre-specified HER2 activating mutations across tumor types. -To assess the safety and tolerability of T-DXd. -To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum. -To investigate the immunogenicity of T-DXd.;Primary end point(s): Confirmed objective response rate by RECIST v1.1 based on independent central review (ICR).;Timepoint(s) of evaluation of this end point: An average of approximately 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of response (DoR) based on ICR assessment. 2) Disease control rate (DCR) based on ICR assessment. 3) Progression free survival (PFS) based on ICR assessment. 4) Confirmed Objective Response Rate (ORR) based on investigator assessment. 5) Overall survival (OS). 6) Occurrence of adverse events (AEs) and serious adverse events (SAEs). 7) Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181. 8) The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.;Timepoint(s) of evaluation of this end point: 1) An average of approximately 12 months. 2) An average of approximately 12 months. 3) An average of approximately 12 months. 4) An average of approximately 12 months. 5) An average of approximately 20 months. 6) An average of approximately 14 months. 7) An average of approximately 14 months. 8) An average of approximately 14 months. | — |
Countries
Belgium, Denmark, France, Italy, Japan, Korea, Republic of, Spain, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed