Participants with locally advanced unresectable or metastatic cancer will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).

HER3-DXd (Patritumab Deruxtecan)

The primary objective of the study is to assess the efficacy of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. Secondary objectives include the assessment of safety and tolerability, efficacy, and pharmacokinetics of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy will also be evaluated.

• Histologically or cytologically documented metastatic or locally advanced nonsquamous NSCLC not amenable to curative surgery or radiation
• Documentation of absence of actionable driver mutation (ie, ALK rearrangement, BRAF V600E mutation, EGFR-activating mutations [exon 19 deletion or L858R mutation], EGFR exon 20 insertion mutation, HER2 mutation, KRAS G12C mutation, MET exon 14 skipping mutation, NTRK 1/2/3 gene fusion, RET not required for Screening.
• Relapsed or disease progression after receiving only anti-PD-(L)1 and PBC (ie, platinum doublet) administered in combination or sequentially for metastatic disease

• Receiving chronic systemic corticosteroids dosed at >10 mg prednisone daily or equivalent;
• Symptomatic or untreated brain metastases;
• Clinically severe respiratory compromise (based on the investigator’s assessment) resulting from intercurrent pulmonary illnesses including, but not limited to, the following: a. Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, or pleural effusion). b. Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjogren’s syndrome, and sarcoidosis) where there is documented or a suspicion of pulmonary involvement at the time of screening. c. Prior complete pneumonectomy.