A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations
Condition: Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast
MeSH terms: Neoplasms
Intervention: Trastuzumab deruxtecan
Intervention description: Trastuzumab deruxtecan (T-DXd) by intravenous infusion
Intervention MeSH terms: Trastuzumab; Trastuzumab deruxtecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: None (open-label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: HER2; T-DXd; DS-8201a; Trastuzumab Deruxtecan; Metastatic; Solid Tumors; Histology Agnostic

Summary:

      This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and
      safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring
      specific HER2 activating mutations regardless of tumor histology. The target population are
      patients who have progressed following prior treatment or who have no satisfactory
      alternative treatment options, including approved second line therapies in the specific tumor
      type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative
      methods. Prior HER2 targeting therapy is permitted.
    

Eligibility 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 (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

        Exclusion Criteria:

          -  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.