Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum Based Chemotherapy (TROPION-Lung05)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04484142

Enrollment

137

Registered

2020-07-23

Start date

2021-03-30

Completion date

2026-02-04

Last updated

2026-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-small Cell Lung Cancer

Keywords

Metastatic Non-small Cell Lung Cancer, Advanced Metastatic Non-small Cell Lung Cancer, Non-small Cell Lung Cancer, DS-1062a, Datopotamab Deruxtecan

Brief summary

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

Detailed description

This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC with actionable genomic alterations and who have been previously been treated with 1 platinum-containing therapy and 1 or more lines of targeted therapy. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all participants either have been followed for at least 9 months after the start of study treatment or have discontinued from the study, whichever occurs first.

Interventions

DRUGDS-1062a

DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Participants eligible for inclusion in the study must meet all inclusion criteria for this study. * Sign and date the inform consent form (ICF) prior to the start of any study- specific qualification procedures. * Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements) * Has pathologically documented NSCLC that: 1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition). 2. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET. KRAS mutations in the absence of any of the genomic alterations specified above will be excluded. Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for enrollment. Participants who have not received osimertinib should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase inhibitor (TKI), unless the participant is already known to be positive with document results for this mutation or unless osimertinib is not locally approved. * Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. * Participant must meet the following for advanced or metastatic NSCLC: 1. Has been treated with at least one but no more than two cytotoxic agent-containing therapy in the metastatic setting: * One platinum-containing regimen (either as monotherapy or combination therapy). * May have received up to one additional line of cytotoxic agent-containing therapy. * Those who received a platinum-containing regimen as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease. 2. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent). 3. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally approved for the participant's applicable genomic alteration at the time of screening: * Those who received a targeted agent for the applicable genomic alterations in the study as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alterations (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease. * Participants who have been treated with a prior TKI must receive additional targeted therapy, if clinically appropriate, for the genomic alterations that are considered amenable or the participant will not be allowed in the study. * Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the mandatory biopsy collected during screening. * Measurable disease based on local imaging assessment using RECIST v1.1. * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

Exclusion criteria

Participants meeting any

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)	From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months.	ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary

Measure	Time frame
Duration of Response (DOR)	From baseline up to approximately 24 months
Progression-free Survival (PFS)	From baseline up to approximately 24 months
Overall Survival (OS)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Maximum Concentration (Cmax)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)	From baseline up to approximately 24 months
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)	From baseline up to approximately 24 months
Percentage of Participants Who Reported Treatment-emergent Adverse Events (TEAE)	From baseline up to approximately 24 months

Countries

France, Germany, Hungary, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United States

Contacts

STUDY_DIRECTORGlobal Clinical Leader

Daiichi Sankyo

Participant flow

Recruitment details

A total of 137 participants who met all inclusion criteria and no exclusion criteria were enrolled to receive Dato-DXd treatment in 50 clinical sites, North America= 15, Europe= 14, Asia Pacific= 21.

Participants by arm

Arm	Count
Dato DXd 6.0 mg/kg Q3W Participants received an intravenous (IV) infusion of Dato DXd administered at a dose of 6.0 mg/kg every 3 weeks (Q3W) on Day 1 of each 21-day cycle.	137
Total	137

Baseline characteristics

Characteristic	Dato DXd 6.0 mg/kg Q3W
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	46 Participants
Age, Categorical Between 18 and 65 years	91 Participants
Age, Continuous	59.5 years STANDARD_DEVIATION 11.15
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	78 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	15 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	43 Participants
Sex: Female, Male Female	83 Participants
Sex: Female, Male Male	54 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	68 / 137
other Total, other adverse events	135 / 137
serious Total, serious adverse events	34 / 137

Outcome results

Primary

Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)

ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time frame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months.

Population: Outcome Measure was assessed in the Full Analysis Set, which includes all subjects who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Dato DXd 6.0 mg/kg Q3W	Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)	35.8 percentage of participants

Secondary