CTRI/2025/02/080765 [Registered on: 18/02/2025] Trial Registered Prospectively
Last Modified On:
26/03/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Other
Public Title of Study
A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Scientific Title of Study
A Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants with EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer whose Disease has Progressed on Prior Osimertinib Treatment
Parexel International Clinical Research Private Limited
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU – 560103, Karnataka, INDIA
India Armenia Belgium Brazil Canada China France Germany Greece Israel Italy Japan Malaysia Philippines Poland Republic of Korea Singapore Spain Taiwan Thailand United Kingdom United States of America Viet Nam Hong Kong
Room No.-CPE donning room Department of Radiation Oncology, Medical Oncology division, Ground Floor, Sijua Patrapada, Bhubaneswar-751019, Odisha, India. Khordha ORISSA
06742476789 06742476789 Deepak.scb2006@gmail.com
Dr Ayyagari Santa
Basavatarakam Indo American Cancer Hospital & Research Institute
Room No.116,Clinical Trial division, Oncology Department, Road No 10, Banjara hills, Hyderabad -500034, Telangana, India Hyderabad TELANGANA
4023550015 4023550015 santa_a2002@yahoo.com
Dr Nirmal Raut
Bhaktivedanta Hospital and Research Institute
Room No.3rd Floor,Medical Research Department, B wing division, Srishti Complex,Bhaktivedanta Swami Marg, Mira Road (East) Thane-401107 Thane MAHARASHTRA
9930398156 9930398156 pinirmal123@gmail.com
Dr Srinivas K G
Bharath Hospital and Institute of Oncology
Room No.-438,Department Name: T-CoRE (Translational Cente for Oncology Research),Oncology division, Outer ring Road, Hebbal, Mysuru-570017, Karnataka, India Mysore KARNATAKA
8212300638 8212300638 drsrinivaskg2020@gmail.com
Dr Rohit Dominic Jawahar Rebello
GBH General Hospital & GBH Memorial Cancer Hospital
Room No.1st floor, Clinical research department, Near Transport Nagar, Airport Road, Bedwas, Udaipur -313002. Udaipur RAJASTHAN
Department-Medical Oncology
Ground floor ,Room no - OPD -01, Hazaribagh Road, Kokar, Ranchi, Jharkhand, 834001, India. Ranchi JHARKHAND
6202700645 6202700645 ksoncologist@gmail.com
Dr Nilesh Ashok Dhamne
Kolhapur Cancer Centre (KCC)
OPD No-2,Medical Oncology department and division, A/p. R. S. No. 238, opp. Mayur Petrol Pump, Gokul Shirgaon, Kolhapur, Maharashtra-416234 India Kolhapur MAHARASHTRA
02677990 02677990 dr.nilesh.gmc@gmail.com
Dr Bipinesh Sansar
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Room No-D and T block, 1st Floor CRS department, Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus, Varanasi, Uttar Pradesh, 221005, India. Varanasi UTTAR PRADESH
0542-2517699 0542-2517699 bipinesh04@yahoo.co.in
Dr Anoop T M
Regional Cancer Centre, Medical College Campus
Room No. E 306, Medical Oncology Department, E clinic (Chest and Gastrointestinal), Thiruvananthapuram, Kerala - 695011 Thiruvananthapuram KERALA
0471252 2543 0471252 2543 dranooptm@yahoo.co.in
Dr Rakesh Kumar Mishra
Sanjeevani CBCC USA Cancer Hospital
Roon No:02,Medical Oncologist Department, Division-Unit 2,Ground floor, In front of Jain Mandir, Dawada Colony, Pachpedi Naka, Raipur, 492001. Raipur CHHATTISGARH
7714081010 7714081010 mishra.rakesh0101@gmail.com
Dr Bharat Ashok Vaswani
Sujan surgical cancer hospital and ACF
52/B, Room No.-Basment PI chamber Clinical Trial department, Oncology division,Shankar Nagar, Main Road, Amravati,444606 Amravati MAHARASHTRA
Room No. 10506 and 10507, Clinical Trial division, A-block upper department, No. 54, Dr Sankaran Road Namakkal Namakkal Tamil Nadu - 637001 India Namakkal TAMIL NADU
(1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Carboplatin
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
Comparator Agent
Cisplatin
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
Intervention
Dato-DXd
Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met
Intervention
Osimertinib
Participants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
Comparator Agent
Pemetrexed
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Histologically or cytologically confirmed non squamous NSCLC.
Must have evidence of documented pre existing EGFRm information EGFRm known to be associated with epidermal growth factor receptor EGFR tyrosine kinase inhibitor TKis sensitivity Ex19de, L858R, G719X, S768I, or L861Q, either alone or in combination with other EGFR mutations, which may include T790M.
Documented extra cranial radiologic progression on prior osimertinib monotherapy as most recent line of treatment in the adjuvant, locally advanced, or metastatic setting.
Less than or equal to less than 2 prior lines of EGFR TKIs osimertinib is the only permitted prior third generation EGFR TKI.
At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
World Health Organization WHO Eastern Cooperative Oncology Group ECOG performance status of 0 or 1.
Adequate bone marrow reserve and organ function within 7 days before randomization.
ExclusionCriteria
Details
Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti cancer therapy in the metastatic setting. Platinum based chemotherapy in non metastatic setting within 12 months prior to randomization.
History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD pneumonitis, cardiac disease.
Has significant third space fluid retention example eg., ascites or pleural effusion as judged by the investigator and is not amenable for required repeated drainage.
History of non infectious ILD pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD pneumonitis, or has suspected ILD pneumonitis that cannot be ruled out by imaging at screening.
Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
Unstable spinal cord compression and or unstable brain metastases.
Participants with symptomatic brain metastases including leptomeningeal involvement.
Clinically significant corneal disease.
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
Has known human immunodeficiency virus (HIV) infection that is not well controlled.
Method of Generating Random Sequence
Other
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Progression free Survival (PFS)
PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.
Up to 2.5 years.
Secondary Outcome
Outcome
TimePoints
Overall Survival (OS)
OS is defined as time from randomization until the date of death due to any cause.
Up to 3.5 years
Central Nervous System Progression-free Survival (CNS PFS)
CNS PFS is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR confirmed CNS modified RECIST v1.1 progression.
Up to 2.5 years
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1.
Up to 2.5 years
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause.
Up to 2.5 years
Progression-free Survival-2 (PFS-2)
PFS2 is defined as the time from randomization to the earliest of the progression event (following the initial investigator assessed progression), after first subsequent therapy, or death.
Up to 3.5 years
Objective Response Rate (ORR) Using CNS Modified RECIST v1.1
ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, using CNS modified RECIST v1.1.
Up to 2.5 years
Duration of Response (DoR) Using CNS Modified RECIST v1.1
DoR is defined as the time from the date of first documented response until date of documented progression or death due to any cause using CNS modified RECIST v1.1.
Up to 2.5 years
Time to Deterioration in Pulmonary Symptoms
Time to deterioration (in pulmonary symptoms [dyspnea, cough, and chest pain]) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Up to 3.5 years
Time to Deterioration in Physical Functioning
Time to deterioration in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form 8c will be evaluated. Time to deterioration (in physical functionating) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Up to 3.5 years
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)
Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172 will be reported. Time to deterioration (in GHS/QoL) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.
Up to 3.5 years
Pharmacokinetics (PK) of Dato-DXd
Concentration of Dato-DXd, total anti-TROP2 antibody and DXd in plasma.
Up to 3.5 years
Immunogenicity of Dato-DXd
Presence of antidrug antibody (ADAs) for Dato-DXd (confirmatory results: positive or negative, titers)
Up to 3.5 years
Target Sample Size
Total Sample Size="630" Sample Size from India="39" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
03/03/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
25/10/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="3" Months="5" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
This is a Phase III, open-label, sponsor-blind, randomized, 3-arm, multicenter study assessing the effects of Dato-DXd monotherapy and Dato-DXd in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFRm locally advanced or metastatic NSCLC whose disease has progressed on prior osimertinib treatment. The study will be conducted at approximately 280 sites globally across an estimated 26 countries. The proposed dual primary objectives are to demonstrate the superiority of Dato-DXd with and without osimertinib compared to chemotherapy in terms of PFS assessed by BICR. Key secondary efficacy endpoints are OS and CNS PFS. The safety and tolerability profile of Dato-DXd with or without osimertinib versus chemotherapy will also be evaluated.