A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC (DL-05)

AstraZeneca

Status and phase: Active, not recruiting; Phase 2

Conditions: HER2-mutant Non-Small Cell Lung Cancer

Treatments: Drug: Trastuzumab deruxtecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT05246514

D7811C00001

Details and patient eligibility

About

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

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 1 patient group

T-DXd arm

Experimental group

Description:

Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.

Treatment:

Drug: Trastuzumab deruxtecan