Unresectable, locally advanced, or metastatic Non-Small Cell Lung Cancer with HER2 exon 19 or 20 mutations MedDRA version: 24.0 Level: PT Classification code 10084787 Term: HER2 mutant non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
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 (locally or centrally tested) - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 247 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 203
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) - Clinically active brain metastases, defined as untreated AND/OR symptomatic, or requiring therapy to control associated symptoms. All participants with brain metastases must have previously completed local therapy. - 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 |
|---|---|
| Main Objective: To assess the efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) in participants with unresectable, locally advanced, or metastatic NSCLC harboring HER2 exon 19 or 20 mutations.;Secondary Objective: - To assess efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of Overall Survival (OS). - To assess efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab in terms of PFS by investigator assessment, Objective Response Rate (ORR), Duration of Response (DoR), time to second progression or death (PFS2), & landmark analysis of PFS12 and OS24 - To assess efficacy of T-DXd relative to platinum with pemetrexed plus pembrolizumab by assessment of CNS-PFS (per RECIST 1.1). - To assess safety and tolerability of T-DXd compared to platinum with pemetrexed plus pembrolizumab. - To assess PK of T-DXd, total anti-HER2 antibody and DXd in serum. - To investigate immunogenicity of T-DXd. - To assess benefit of T-DXd relative to platinum with pemetrexed plus pembrolizumab with patient-reported pulmonary symptoms associated with NSCLC. - To describe patient-reported tolerability of T-DXd as compared to platinum with pemetrexed plus pembrolizumab.;Primary end point(s): Progression Free Survival (PFS) defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause.;Timepoint(s) of evaluation of this end point: Until progression or death, assessed up to approximately 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) defined as time from randomization until date of death due to any cause. 2. PFS by investigator assessment defined as time from randomization until progression as assessed by investigator (per RECIST 1.1) or death due to any cause. Objective Response Rate (ORR) and Duration of Response (DoR) by BICR and Investigator assessment per RECIST 1.1. ORR is defined as proportion of participants who have a complete response (CR) or partial response (PR). DoR is defined as time from date of first documented response until date of documented progression. PFS2 is defined as time from randomization to second progression on next-line of treatment as assessed by investigator or death due to any cause. PFS12 is the landmark of PFS which is defined as proportion of participants alive and progression-free at 12 months as assessed by BICR and investigator. OS24 is the landmark of OS defined as proportion of patients alive at 24 months 3. CNS-PFS defined as time from randomization until CNS-progression (RECIST 1.1) as assessed by BICR or death due to any cause in absence of CNS progression. 4. AEs, SAEs, changes from baseline in laboratory parameters, vital signs, ECG, ECHO/MUGA results 5. Pharmacokinetics (PK) of T-DXd and serum concentration of T-DXd, total anti-HER2 antibody and DXd 6. Presence of ADAs for T-DXd 7. Time to sustained deterioration in pulmonary symptoms while on treatment using NSCLC-Symptom Assessment Questionnaire (SAQ) 8. Patient Reported Tolerability will be described among participants using the following outcomes: Symptomatic AEs (assessed by PRO-CTCAE and EORTC Item Library), Overall Side Effect Bother (reported on Patient’s Global Impression of Treatment Tolerability (PGI-TT)), Physical Function (based on EORTC-QLQ-30);Timepoint(s) of evaluation of this end point: 1. Until death, assessed up to approximately 28 months. 2. PFS by investigator assessment: Until progression, assessed up to | — |
Countries
Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Taiwan, Türkiye, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed