Clinical trial NCT06417814: 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
Official title: 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 (TROPION-Lung15)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Non-small Cell Lung Cancer
Keywords: Epidermal growth factor receptor gene mutation
Standard of Care
Locally, advanced carcinoma
Metastatic carcinoma
Non-small cell lung cancer
Dato-dxd
Datopotamab deruxtecan
Osimertinib
Tagrisso
Pemetrexed
Carboplatin
Cisplatin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2024-05-16
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

Detailed description: This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment.

Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups:

1. Dato-DXd + osimertinib combination therapy
2. Dato-DXd monotherapy
3. Platinum-based doublet chemotherapy

Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met.

After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.

Eligibility criteria: Inclusion Criteria:

* 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 \[Ex19del, L858R, G719X, S768I, or L861Q\], 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 (\<=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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression free Survival (PFS)
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 3.5 years
measure: Central Nervous System Progression-free Survival (CNS PFS)
timeFrame: Up to 2.5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 2.5 years
measure: Duration of Response (DoR)
timeFrame: Up to 2.5 years
measure: Progression-free Survival-2 (PFS-2)
timeFrame: Up to 3.5 years
measure: Objective Response Rate (ORR) Using CNS Modified RECIST v1.1
timeFrame: Up to 2.5 years
measure: Duration of Response (DoR) Using CNS Modified RECIST v1.1
timeFrame: Up to 2.5 years
measure: Time to Deterioration in Pulmonary Symptoms
timeFrame: Up to 3.5 years
measure: Time to Deterioration in Physical Functioning
timeFrame: Up to 3.5 years
measure: Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)
timeFrame: Up to 3.5 years
measure: Pharmacokinetics (PK) of Dato-DXd
timeFrame: Up to 3.5 years
measure: Immunogenicity of Dato-DXd
timeFrame: Up to 3.5 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Research Site
state: Arkansas
city: Duarte
country: United States
facility: Research Site
state: California
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: La Jolla
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state: California
city: Los Angeles
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city: San Diego
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state: California
city: Fort Collins
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state: Colorado
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state: Michigan
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state: Nebraska
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city: Bronx
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state: New York
city: New York
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state: New York
city: New York
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city: Charleroi
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city: Edegem
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city: Gent
country: Belgium
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city: Porto Alegre
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city: Rio de Janeiro
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city: Rio de Janeiro
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state: Ontario
city: Toronto
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state: Ontario
city: Toronto
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state: Ontario
city: Montreal
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state: Quebec
city: Quebec
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facility: Research Site
city: Baoding
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
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city: Bengbu
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city: Changchun
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city: Changchun
country: China
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city: Changsha
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Deyang
country: China
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city: Ganzhou
country: China
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city: Guangzhou
country: China
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city: Hangzhou
country: China
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city: Hangzhou
country: China
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city: Hefei
country: China
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city: Hengyang
country: China
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city: Huaian
country: China
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city: Jinan
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Luzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shantou
country: China
facility: Research Site
city: Shenyang
country: China
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city: Shenyang
country: China
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city: Tianjin
country: China
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city: Tianjin
country: China
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city: Weifang
country: China
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city: Wuhan
country: China
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city: Zhengzhou
country: China
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city: Zhengzhou
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: ANGERS Cedex 9
country: France
facility: Research Site
city: Avignon
country: France
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city: Bordeaux
country: France
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city: Caen
country: France
facility: Research Site
city: Lille Cedex
country: France
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city: Montpellier
country: France
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city: Nantes
country: France
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city: Paris Cedex 14
country: France
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city: Paris
country: France
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city: Pessac
country: France
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city: Quimper
country: France
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city: Toulon Armees
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Berlin-Zehlendorf
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
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city: Großhansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
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city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
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city: Kempten
country: Germany
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city: Löwenstein
country: Germany
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city: Nürnberg
country: Germany
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city: Oldenburg
country: Germany
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Heraklion
country: Greece
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city: Thessaloniki
country: Greece
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city: Thessaloniki
country: Greece
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city: Thessaloniki
country: Greece
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city: Thessaloniki
country: Greece
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city: Hong Kong
country: Hong Kong
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city: Hong Kong
country: Hong Kong
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city: Shatin
country: Hong Kong
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city: Amravati
country: India
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city: Bhubaneswar
country: India
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city: Hyderabad
country: India
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city: Kolhapur
country: India
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city: Mumbai
country: India
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city: Mysuru
country: India
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city: Namakkal
country: India
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city: Pune
country: India
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city: Raipur
country: India
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city: Rajasthan
country: India
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city: Ranchi
country: India
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city: Thane
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city: Trivandrum
country: India
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city: Varanasi
country: India
facility: Research Site
city: Beer Sheva
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
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city: Tel Aviv
country: Israel
facility: Research Site
city: Bari
country: Italy
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city: Milano
country: Italy
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city: Misterbianco
country: Italy
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city: Monza
country: Italy
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city: Napoli
country: Italy
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city: Orbassano
country: Italy
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city: Padova
country: Italy
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city: Parma
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city: Perugia
country: Italy
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city: Roma
country: Italy
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city: Rozzano
country: Italy
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city: Verona
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Iruma-Gun
country: Japan
facility: Research Site
city: Iwakuni-shi
country: Japan
facility: Research Site
city: Kobe
country: Japan
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city: Koto-ku
country: Japan
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city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
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city: Matsuyama-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-Sayama
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Toyoake-shi
country: Japan
facility: Research Site
city: Utsunomiya-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Alor Setar
country: Malaysia
facility: Research Site
city: Cheras
country: Malaysia
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Perai
country: Malaysia
facility: Research Site
city: Petaling Jaya
country: Malaysia
facility: Research Site
city: Selangor
country: Malaysia
facility: Research Site
city: Amersfoort
country: Netherlands
facility: Research Site
city: Harderwijk
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
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city: Bacolod
country: Philippines
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city: Cebu City
country: Philippines
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city: Davao City
country: Philippines
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city: Manila
country: Philippines
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city: Quezon
country: Philippines
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city: Quezon
country: Philippines
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city: San Juan
country: Philippines
facility: Research Site
city: Katowice
country: Poland
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city: Krakow
country: Poland
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city: Olsztyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Braga
country: Portugal
facility: Research Site
city: Porto
country: Portugal
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city: Porto
country: Portugal
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Singapore
country: Singapore
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city: Singapore
country: Singapore
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city: Singapore
country: Singapore
facility: Research Site
city: Barakaldo
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
facility: Research Site
city: El Palmar
country: Spain
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city: L'Hospitalet de Llobregat
country: Spain
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city: La Coruna
country: Spain
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city: Madrid
country: Spain
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city: Majadahonda
country: Spain
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city: Malaga
country: Spain
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city: Palma de Mallorca
country: Spain
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city: Pamplona
country: Spain
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city: Santander
country: Spain
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city: Santiago De Compostela-Coruña
country: Spain
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city: Sevilla
country: Spain
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city: Valencia
country: Spain
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city: Valencia
country: Spain
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city: Valladolid
country: Spain
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city: Changhua City
country: Taiwan
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city: Kaohsiung City
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Tainan City
country: Taiwan
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city: Tainan
country: Taiwan
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city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon-Kaen
country: Thailand
facility: Research Site
city: Pathumthani
country: Thailand
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Middlesbrough
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
Study officials:
References: