DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations
Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease. The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
454
Trastuzumab Deruxtecan administered by intravenous infusion
Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion
Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
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.
Time frame: Until progression or death, assessed up to approximately 12 months
Overall Survival (OS)
Defined as time from randomization until the date of death due to any cause.
Time frame: Until death, assessed up to approximately 28 months.
Progression Free Survival (PFS) by investigator assessment
Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause.
Time frame: Until progression, assessed up to approximately 12 months
Objective Response Rate (ORR)
Defined as the proportion of participants who have a complete response (CR) or partial response (PR) as assessed by Blinded Independent Central Review (BICR) and investigator according to RECIST 1.1
Time frame: Until progression, assessed up to approximately 12 months
Duration of Response (DoR)
Defined as the time from the date of first documented response until date of documented progression as assessed by Blinded Independent Central Review (BICR) and investigator assessment according to RECIST 1.1.
Time frame: Until progression, assessed up to approximately 12 months
Time to second progression or death (PFS2)
Defined as the time from randomization until second progression on next-line of treatment as assessed by investigator at the local site using assessments conducted per local standard clinical practice, or death due to any cause.
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Pembrolizumab administered by intravenous infusion
Pemetrexed administered by intravenous infusion
Research Site
Anchorage, Alaska, United States
Research Site
Los Alamitos, California, United States
Research Site
Los Angeles, California, United States
Research Site
Orange, California, United States
Research Site
San Francisco, California, United States
Research Site
Santa Monica, California, United States
Research Site
Silver Spring, Maryland, United States
Research Site
Boston, Massachusetts, United States
Research Site
Ann Arbor, Michigan, United States
Research Site
Basking Ridge, New Jersey, United States
...and 120 more locations
Time frame: Assessed up to approximately 20 months
Landmark analysis of PFS (PFS12)
Defined as proportion of participants alive and progression-free at 12 months, as assessed by Blinded Independent Central Review (BICR) and investigator.
Time frame: Assessed up to approximately 12 months
Landmark analysis of OS (OS24)
Defined as proportion of participants alive at 24 months
Time frame: Assessed up to approximately 24 months
Central Nervous System (CNS) - Progression Free Survival (PFS)
Defined as time from randomization until Central Nervous System (CNS) progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause in the absence of CNS progression.
Time frame: Until CNS progression or death, assessed up to approximately 12 months
Safety and tolerability of T-DXd versus Standard of Care treatment
Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, ECG, and ECHO/MUGA scan results.
Time frame: Until progression or death, assessed up to approximately 28 months
Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum
Serum concentration of T-DXd, total anti-HER2 antibody and DXd.
Time frame: Up to cycle 4, approximately 12 weeks
Immunogenicity of T-DXd
Presence of anti-drug antibodies (ADAs) for T-DXd.
Time frame: Until progression, assessed up to approximately 13 months
Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer
Time to sustained deterioration in pulmonary symptoms (cough, dyspnea, chest pain) while on treatment using the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ).
Time frame: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using symptomatic AEs
Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by the Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library.
Time frame: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using overall side-effect bother
Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the Patient's Global Impression of Treatment Tolerability (PGI-TT) while on treatment.
Time frame: Until progression, assessed up to approximately 13 months
Patient-reported tolerability of T-DXd described using physical function
Physical Function: The proportion of participants with maintained or improved physical function while on treatment, based on the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC-QLQ-C30) physical functioning scale.
Time frame: Until progression, assessed up to approximately 13 months