Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

NCT04526691 | Active Not Recruiting Phase 1 FDA Drug

• 5 other identifiers: DS1062-A-U1022020-006047-25jRCT2031200193KEYNOTE-B43MK-3475-B43
• Study Type: interventional
• Target: 145
• Locations: 5 countries
• Sites: 24

Brief Summary

This study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic non-small cell lung cancer.

Conditions

Advanced or Metastatic NSCLC

Keywords

Advanced or Metastatic NSCLC; Datopotamab deruxtecan (Dato-DXd); Pembrolizumab; KEYNOTE; DS-1062a

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs)

  Baseline up to Cycle 1 (Days 1 to 21) for DLTs and up to 28 days after last dose for TEAEs, up to approximately 30 months post-dose

Secondary Outcomes (8)

• Objective Response Rate

  Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose

• Duration of Response

  From first objective response (confirmed CR or PR) to PD or death (whichever occurs first), up to approximately 30 months post-dose

• Progression-free Survival

  Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose

• Overall Survival

  Baseline up to death (any cause), up to approximately 30 months post-dose

• Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a

  Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)

Study Arms (1)

Datopotamab deruxtecan (Dato-DXd)

EXPERIMENTAL

Dose Escalation and Dose Expansion: Datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic NSCLC

Drug: Datopotamab deruxtecan; Drug: KEYTRUDA®; Drug: Carboplatin; Drug: Cisplatin

Interventions

Datopotamab deruxtecan DRUG

Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (starting datopotamab deruxtecan dose of 4.0 mg/kg)

Also known as: Dato-DXd

Datopotamab deruxtecan (Dato-DXd)

KEYTRUDA® DRUG

Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W)

Also known as: pembrolizumab

Datopotamab deruxtecan (Dato-DXd)

Carboplatin DRUG

Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)

Datopotamab deruxtecan (Dato-DXd)

Cisplatin DRUG

Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m\^2)

Datopotamab deruxtecan (Dato-DXd)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed at diagnosis of NSCLC that:
• Is advanced or metastatic.
• Participants with non-squamous histology must have documented negative test results for actionable EGFR and ALK genomic alterations. Participants with squamous histology are required to undergo testing for EGFR and ALK genomic alterations if they are nonsmokers or under the age of 40 years.
• Has either documented negative or unknown test results for actionable genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver kinases.
• Participants with tumors that harbor KRAS mutations are eligible for this study.
• Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other kinases are eligible for the study.
• Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC.
• Must meet the following prior therapy requirements for advanced or metastatic NSCLC:
• Dose escalation (all cohorts): Has received ≤2 lines of prior anticancer therapy for locally advanced or metastatic NSCLC.
• Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4 directed immunotherapy and may or may not have been treated with systemic chemotherapy for advanced or metastatic NSCLC.
• Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m\^2): Has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC.
• Willing and able to undergo a mandatory tumor biopsy.
• Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers.
• Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1.
• Is not a candidate for surgical resection or chemoradiation with curative intent.

You may not qualify if:

• Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Received a live vaccine within 30 days prior to the first dose of study treatment.
• Active, known, or suspected autoimmune disease.
• Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications, except for managing AEs.
• Prior organ transplantation, including allogeneic tissue or solid organ transplantation.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
• History of another primary malignancy (beyond NSCLC) except for:
• Malignancy treated with curative intent and with no known active disease for ≥3 years.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (24)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Johns Hopkins Kimmel Cancer Center

Washington D.C., District of Columbia, 20016, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Johns Hopkins Kimmel Cancer Center at Bayview

Baltimore, Maryland, 21224, United States

Location

The Skip Viragh Outpatient Cancer Building

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Quantum Santa Fe

Santa Fe, New Mexico, 87505, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Instituto Europeo Di Oncologica

Milan, 20141, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20052, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia

Naples, 80131, Italy

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Showa Medical University Hospital

Tokyo, 142-8555, Japan

Location

H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)

Barcelona, 08035, Spain

Location

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

(CIOCC-START) Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Puerta de Hierro

Majadahonda, 28222, Spain

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital NTUH

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and dose expansion model

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 26, 2020
• Study Start: September 15, 2020
• Primary Completion: April 15, 2026
• Study Completion: April 15, 2026
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (9); ES (5); TW (4); IT (3); JP (3)