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)

NCT ID: NCT04526691

Last Updated: 2025-05-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2026-04-15

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.

Detailed Description

The primary objective of this study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without 4 cycles of platinum chemotherapy in participants with advanced or metastatic NSCLC who have either been previously treated or are treatment naïve in a metastatic setting.

Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with 200 mg fixed-dose pembrolizumab in 6 study cohorts. This study will be conducted sequentially and dose escalation will occur according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0 mg/kg) and from 2-drug combination (Dato-DXd and pembrolizumab) to 3-drug combination regimen (Dato-DXd, pembrolizumab, and carboplatin or cisplatin).

Conditions

Advanced or Metastatic NSCLC

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Datopotamab deruxtecan (Dato-DXd)

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

Group Type: EXPERIMENTAL

Datopotamab deruxtecan

Intervention Type: DRUG

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

KEYTRUDA®

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

Datopotamab deruxtecan

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

Intervention Type: DRUG

KEYTRUDA®

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Other Intervention Names

Dato-DXd; pembrolizumab

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Mayo Clinic

Scottsdale, Arizona, United States

City of Hope

Duarte, California, United States

Johns Hopkins Kimmel Cancer Center

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

Mayo Clinic

Jacksonville, Florida, United States

Johns Hopkins Kimmel Cancer Center at Bayview

Baltimore, Maryland, United States

The Skip Viragh Outpatient Cancer Building

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Quantum Santa Fe

Santa Fe, New Mexico, United States

NEXT Oncology

San Antonio, Texas, United States

Instituto Europeo Di Oncologica

Milan, , Italy

Azienda Ospedaliera San Gerardo

Monza, , Italy

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

Naples, , Italy

National Cancer Center Hospital East

Chiba, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Showa Medical University Hospital

Tokyo, , Japan

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

Barcelona, , Spain

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

(CIOCC-START) Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Puerta de Hierro

Majadahonda, , Spain

Chung Shan Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital NCKUH

Tainan City, , Taiwan

National Taiwan University Hospital NTUH

Taipei, , Taiwan

Countries

United States; Italy; Japan; Spain; Taiwan

Other Identifiers

2020-006047-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

jRCT2031200193

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-B43

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-B43

Identifier Type: OTHER

Identifier Source: secondary_id

DS1062-A-U102

Identifier Type: -

Identifier Source: org_study_id