A Phase 3 interventional study of Patritumab Deruxtecan and Platinum-based chemotherapy in Nonsquamous Non-small Cell Lung Cancer, EGFR L858R and EGFR Exon 19 Deletion, sponsored by Daiichi Sankyo. Active, not recruiting at 182 sites in 21 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-27.
Sponsored by Daiichi Sankyo · Phase 3, Interventional, and Treatment
Disease progression is typical for patients with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). Standard platinum-based chemotherapy offers limited efficacy and an unfavorable safety profile. There is an urgent need for more effective and tolerable therapies for patients with EGFRm NSCLC who have exhausted available targeted therapies. Clinical evidence suggests that patritumab deruxtecan constitutes a promising investigational therapy for patients with EGFRm NSCLC.
Patritumab deruxtecan (HER3-DXd, U3-1402) is an antibody-drug conjugate (ADC) comprising an anti-HER3 mAb linked to a topoisomerase I inhibitor that is in clinical development for patients with NSCLC, metastatic breast cancer, and colorectal cancer.
The primary objective of the current study is to compare the efficacy of patritumab deruxtecan versus platinum-based chemotherapy, as measured by progression-free survival (PFS) and the key secondary endpoint of overall survival (OS), in participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) after failure of third-generation (eg, osimertinib, lazertinib, aumolertinib, alflutinib) EGFR TKI therapy.
Daiichi Sankyo is the lead sponsor of 316 studies on the registry; 35 are open to participants now.
Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Has adequate bone marrow reserve and organ function based on local laboratory evaluation within 14 days prior to randomization:
Exclusion Criteria:
Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to the following:
Participants received patritumab deruxtecan (HER3-DXd) 5.6 milligrams per kilogram (mg/kg), intravenously (IV) on Day 1 of each 21-day cycle (every 3 weeks \[q3W\]) until occurrence of unacceptable toxicity, radiographic or clinical disease progression (PD), withdrawal of consent, physician decision, pregnancy, loss to follow-up or death, whichever occurs first; data cut-off (DCO) date: 31 May 2024.
Drug: Patritumab Deruxtecan
Participants received platinum-based chemotherapy; pemetrexed (500 milligrams per square meter \[mg/m\^2\]) plus either cisplatin (75 mg/m\^2) or carboplatin (target area under the plasma concentration-time curve of 5 \[AUC5\] by using the Calvert formula), IV on Day 1 of each cycle up to 4 cycles or until PD, whichever occurs first. Participants without disease progression after 4 cycles of platinum plus pemetrexed therapy continued treatment with maintenance pemetrexed with no restriction on the number of cycles; data cut-off (DCO) date: 31 May 2024.
Drug: Platinum-based chemotherapy
Intravenous administration, 5.6 mg/kg every 3 weeks (q3W).
Also known as: HER3-DXd, U3-1402
Intravenous, pemetrexed 500 mg/m\^2 plus either cisplatin (75 mg/m\^2) or carboplatin (target area under the plasma concentration time curve of 5 \[AUC5\] by using the Calvert formula) q3W.
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Based on RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
Time frame: Baseline up to approximately 49 months
Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Baseline up to approximately 32 months
Progression-free Survival (PFS) as Assessed by Investigator Review Based on RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
Time frame: Baseline up to approximately 49 months
Progression-free Survival (PFS) as Assessed by Local Standard Clinical Practice
Progression-free survival (PFS) by local standard clinical practice is defined as the time from date of randomization to the documented progression on the first new anticancer therapy (if administered) or death due to any cause, whichever occurred first.
Time frame: Baseline up to approximately 49 months
Objective Response Rate (ORR) as Assessed by BICR and Investigator Review Based on RECIST v1.1
Objective response rate (ORR) is defined as the proportion of participants who have a confirmed best overall response (BOR) of complete response (CR) or partial response (PR).
Time frame: Baseline up to approximately 49 months
Duration of Response (DoR) as Assessed by BICR and Investigator Review Based on RECIST v1.1
Duration of response (DoR) is defined as the time from the first documentation of objective response (CR or PR) to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
Time frame: Baseline up to approximately 49 months
Clinical Benefit Rate (CBR) as Assessed by BICR and Investigator Review Based on RECIST v1.1
Clinical benefit rate (CBR) will be assessed by BICR and Investigator based on RECIST v1.1. CBR is defined as the proportion of participants who have a confirmed BOR of CR, PR, or stable disease (SD) that lasts for at least 180 days.
Time frame: Baseline up to approximately 49 months
Disease Control Rate (DCR) as Assessed by BICR and Investigator Review Based on RECIST v1.1
Disease control rate (DCR) is defined as the proportion of participants who have a confirmed BOR of CR, PR, or SD.
Time frame: Baseline up to approximately 49 months
Time to Response (TTR) as Assessed by BICR and Investigator Review Based on RECIST v1.1
Time to response (TTR) is defined as the time from the date of randomization to the date of the first documentation of response (CR or PR) that is subsequently confirmed.
Time frame: Baseline up to approximately 49 months
Intracranial PFS as Assessed by BICR
Intracranial PFS is defined as the time from the date of randomization to the earlier of the dates of the first documented radiographic intracranial disease progression or death, whichever comes first, as assessed by BICR per CNS-RECIST, in participants with CNS lesion(s) at baseline by BICR per CNS-RECIST.
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in Non-small Cell Lung Cancer - Symptom Assessment Questionnaire
The NSCLC-SAQ will assess disease-related symptom change in patients with NSCLC.
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Change
The PGI-C is a 7-point scale depicting a participant's rating of overall improvement.
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Severity
The PGI-S is a one-item questionnaire that contains six response options.
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Treatment Tolerability
The PGI-TT will capture the patient's overall impression of treatment tolerability.
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
The EORTC-QLQ-C30 will assess the patient's overall quality of life (QoL).
Time frame: Baseline up to approximately 49 months
Mean Change from Baseline in EuroQol Questionnaire-5 dimensions-5 levels (EQ-5D-5L)
The EQ-5D-5L is a standardized instrument that will be used for measuring generic health status required for health technology assessments.
Time frame: Baseline up to approximately 49 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs will be graded by using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
Time frame: Baseline up to approximately 49 months
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.
Time frame: Baseline up to approximately 49 months
Percentage of Participants Who Have Treatment-emergent ADA
The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.
Time frame: Baseline up to approximately 49 months
Showing the first 100 of 182 sites across 21 countries.
Plan to share: Yes — De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting information: Study protocol, Sap, Csr
This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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