Phase II, open-label, multi-centre, multi-cohort trial to evaluate the preliminary efficacy and safety of zongertinib for the treatment of selected HER2-mutated or overexpressed/amplified tumours.

Zongertinib (BI 1810631) 120mg daily per/os.

AvL: cohort 5 is open

• Objective response (OR) defined as the best overall response.
• Duration of objective response.
• Progression-free survival (PFS)

• HER2 overexpression/amplification (with or without HER2 mutations)
• Failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.

• Diagnosis of HER2 mutant NSCLC.
• Previous treatment with any HER2 tyrosine kinase inhibitors (TKIs) including, but not limited to, lapatinib, afatinib, neratinib, or dacomitinib in the advanced or metastatic setting. In the case of use in the adjuvant setting, at least 12 months must have passed prior to the start of trial drug.
• Uncontrolled and/or symptomatic brain metastases or primary brain tumour.
• Known brain metastases if: untreated brain lesions >2.0 cm in size; use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of >2 mg of dexamethasone (or equivalent); brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to subject.
• Known or suspected leptomeningeal disease as documented by the investigator.
• History or presence of uncontrolled cardiovascular abnormalities.