A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

An Open-label, Single-arm, Phase 2 Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for Patients With HER2-mutant Metastatic NSCLC Who Have Disease Progression on or After at Least One-line of Treatment (DESTINY-Lung05)

The purpose of this study is to evaluate the efficacy and safety of T-DXd in participants with HER2 mutant metastatic non-squamous NSCLC.

Inclusion Criteria:

• Pathologically documented metastatic non-squamous NSCLC.
• Has relapsed from or is refractory to at least one-line of anticancer treatment.
• Documented HER2 exon 19 or 20 mutation from central FFPE tumour tissue testing.
• WHO or ECOG performance status of 0 or 1.
• Presence of at least one measurable lesion assessed by the investigator based on RECIST 1.1.
• LVEF ≥ 50% within 28 days before enrolment.

Exclusion Criteria:

• Mixed small cell lung cancer, squamous histology NSCLC, and sarcomatoid histology variant NSCLC.
• Corrected QT interval (QTcF) prolongation to > 470 ms (females) or > 450 ms (males), based on average of the screening triplicate 12-lead ECG.
• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (excluding alopecia) not yet resolved to Grade ≤1 or baseline. Participants with clinically stable chronic Grade 2 toxicity not reasonably expected to be exacerbated by study intervention may be included only after consultation with the AstraZeneca study physician or designee.
• Has been previously treated with HER2-targeted therapies, except for pan-HER class TKIs or has received prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.