Locally advanced or metastatic NSCLC harboring HER2 exon 19 or 20 mutations lungcancer
Conditions
Interventions
Participants will be randomized in a 1:1 ratio to one of the following
interventions: T-DXd (Arm 1) or platinum (cisplatin or carboplatin
up to 4
cycles) with pemetrexed plus pembrolizumab Q3W (Arm 2). Randomization will be
stratified by smoking history and presence of brain metastasis at baseline.
- Participants in Arm 1 (T-DXd) wil
see
note below).
- Participants in Arm 2 (active comparator arm) will receive platinum
chemotherapy (cisplatin or carboplatin) with pemetrexed and pembrolizumab Q3W.
Note: Investigator choice of ci
see note below).
Note: In both arms, participants with objective radiological CNS-PD (based on
RECIST 1.1), who in the investigator*s opinion, continue to receive benefit
from their assigned treatm
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Male and female participants at least 18 years of age - Locally advanced not amenable to curative therapy, or metastatic disease - Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA - Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease - Left ventricular ejection fraction (LVEF) >= 50% - Measurable disease assessed by Investigator based on RECIST v1.1 - Protocol-defined adequate organ function including cardiac, renal, hepatic function - ECOG 0-1 - Having tumour tissue available for central testing
Exclusion criteria
Exclusion criteria: - Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy) - Any clinically active brain metastases; previously treated brain metastases allowed - Active autoimmune or inflammatory disorders - Medical history of myocardial infarction within 6 months prior to randomization - History of non-infectious pneumonitis/ILD, current or suspected ILD - Lung-specific intercurrent clinical significant severe illness - Contraindication to platinum-based doublet chemotherapy or pembrolizumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of PFS by BICR in participants with unresectable, locally advanced, or metastatic NSCLC harboring HER2 exon 19 or 20 mutations. PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomized participants, regardless of whether the participant withdraws from randomized therapy or receives another anticancer therapy. The measure of interest is the HR of PFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of OS. - To further assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab in terms of PFS by investigator assessment, ORR, DoR, PFS2, and landmark analysis of PFS12 and OS24. - To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of CNS-PFS (per RECIST 1.1). - To assess the safety and tolerability of T-DXd as compared to platinum with pemetrexed plus pembrolizumab. - To assess the PK of T-DXd, total anti-HER2 antibody and DXd in serum. - To investigate the immunogenicity of T-DXd. - To assess the benefit of T-DXd relative to platinum with pemetrexed plus pembrolizumab with patientreported pulmonary symptoms associated with NSCLC. - To describe patient-reported tolerability of T-DXd as compared to platinum with pemetrexed plus pembrolizumab. | — |
Countries
Netherlands
Outcome results
None listed