Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Mitogens

Patritumab deruxtecan

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Antineoplastic Agents, Immunological

Study Group 1 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W)

Study Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV every 3 weeks (Q3W)

Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Patritumab Deruxtecan (Fixed dose)

Patritumab deruxtecan will be dosed as an intravenous (IV) infusion administered at Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and subsequent cycles, 6.4 mg/kg administered on Day 1 of each 21-day cycle.

Patritumab Deruxtecan (Up-Titration)

Medical Director

This study is designed to evaluate the antitumor activity of patritumab deruxtecan in participants with metastatic or locally advanced NSCLC with an activating EGFR mutation (exon 19 deletion or L858R) who have received and progressed on or after at least 1 EGFR TKI and 1 platinum-based chemotherapy-containing regimen.

This study will initially randomize participants to one of 2 arms in a 1:1 ratio to receive either a 5.6 mg/kg fixed dose regimen or an up-titration dose regimen of patritumab deruxtecan (HER3-DXd, U3-1402).

HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer

HERTHENA-Lung01: A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

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/

ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

DoR is defined as the time from the first documented confirmed response (CR or PR) to the date of progression or death due to any cause as assessed by BICR and Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

PFS is defined as the time from the start of study treatment to the first documentation of objective progressive disease (PD) per RECIST v1.1 or death due to any cause. PFS will be determined by BICR and by Investigator, respectively.

ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR as assessed by the Investigator per RECIST v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) as assessed by BICR and by the Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.

TTR is defined as the time from the start of study treatment to the date of the first documentation of confirmed response (CR or PR) as assessed by BICR and Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

The best percentage change in the SoD of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.

OS defined as the time from the start of study treatment to the date of death due to any cause.

A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. Adverse events will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo

Safety events are reported from the Safety Analysis Set. Treatment-emergent adverse events are reported per the investigator.

Participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation and who received patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W)

Patritumab Deruxtecan 5.6 mg/kg

Participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation and received a patritumab deruxtecan up-titration regimen

Patritumab Deruxtecan Up-Titration

Total

Age, Continuous

<65 years

≥65 years

<75 years

≥75 years

Age, Customized

Sex: Female, Male

Asian

Black or African-American

Native Hawaiian or Other Pacific Islander

White

Other

Race/Ethnicity, Customized

Demographic and baseline characteristics were reported from the Full Analysis Set.

Contact for Clinical Trial Information

Objective response rate was assessed in the Efficacy Analysis Set.

Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)

Duration of response (BICR)

Duration of response (Investigator)

Duration of response rate was assessed in participants with confirmed CR or PR in the Efficacy Analysis Set.

Duration of Response (DoR)

Progression-free survival (BICR)

Progression-free survival (Investigator)

Progression-free survival was assessed in the Efficacy Analysis Set.

Progression-free Survival (PFS)

Objective Response Rate (ORR) as Assessed by the Investigator

Disease control rate (BICR)

Disease control rate (Investigator)

Disease control rate was assessed in the Efficacy Analysis Set.

Disease Control Rate (DCR)

Time to response (BICR)

Time to response (Investigator)

Time to response rate was assessed in participants with confirmed CR or PR in the Efficacy Analysis Set.

Time to Tumor Response (TTR)

Sum of diameters (BICR)

Sum of diameters (Investigator)

Percentage change in the sum of diameters was assessed in participants with available data in the Efficacy Analysis Set.

Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors

Overall Survival (OS)

Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)

Participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation and who received a patritumab deruxtecan up-titration regimen

Spots Global Cancer Trial Database for patritumab deruxtecan (fixed dose)