Trial Title:
Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer
NCT ID:
NCT06350097
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Osimertinib
Conditions: Keywords:
Non-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Osimertinib
Description:
Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v.
infusion.
Arm 2: Osimertinib 80 mg QD as oral tablet .
Arm group label:
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
Arm group label:
Arm 2: Osimertinib monotherapy
Other name:
Osimertinib: AZD9291
Other name:
Datopotamab Deruxtecan: Dato-DXd
Intervention type:
Drug
Intervention name:
Datopotamab Deruxtecan
Description:
Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.
Arm group label:
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
Other name:
Osimertinib: AZD9291
Other name:
Datopotamab Deruxtecan: Dato-DXd
Summary:
The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in
combination with Datopotamab Deruxtecan (i.v. infusion) compared with osimertinib
(tablet) monotherapy as a first-line therapy in participants with locally advanced or
metastatic EGFRm (Ex19del and/or L858R) NSCLC.
Study details include:
1. The study duration will be event-driven, with an estimated duration of approximately
9 years.
2. Participants may receive study treatment until disease progression, unacceptable
toxicity, or other specific discontinuation criteria are met.
3. The visit frequency will be every 3 weeks during the treatment period.
Note: Participants on osimertinib treatment (osimertinib only arm or who have
discontinued Datopotamab Deruxtecan while are still receiving osimertinib) are required
to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and
then visits every 12 weeks until disease progression, IP discontinuation or primary PFS
DCO. Participants who are receiving osimertinib + Datopotamab Deruxtecan are still
required to attend visit to perform assessment every 3 weeks (q3w) per SoA.
Detailed description:
This is a global Phase III, open-label, randomised, multicentre study assessing the
efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared
with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del
and/or L858R) NSCLC who have not received any prior therapy for advanced disease.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Age
1. Participant must be ≥ 18 years; Participant from Japan must be ≥ 20 years, at the
time of signing the ICF.
Type of Participant and Disease Characteristics
2. Histologically or cytologically documented nonsquamous NSCLC.
3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the
American Joint Committee on Cancer Edition 8) not amenable to curative surgery or
definitive chemoradiation at the time of randomisation.
4. Participants must not have received prior EGFR TKIs or other systemic therapy for
Stage IIIB, IIIC or IV NSCLC.
5. The tumour harbors 1 of the 2 common EGFR mutations known to be associated with
EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other
EGFR mutations.
6. For participants enrolled in randomisation period, mandatory provision of an
unstained, archival tumour tissue sample in a quantity sufficient to allow for
central confirmation of the EGFR mutation status.
7. WHO performance status of 0 or 1.
8. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at
baseline and can be accurately measured at baseline as ≥10 mm in the longest
diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and
is suitable for accurate repeated measurements.
9. Adequate bone marrow reserve and organ function within 7 days before the first dose
of study intervention .
Sex and Contraceptive/Barrier Requirements
10. Male and female Contraceptive use by males or females should be consistent with
local regulations regarding the methods of contraception for those participating in
clinical studies.
Other Inclusion Criteria
11. All races, gender and ethnic groups are eligible for this study.
Exclusion Criteria:
Medical Conditions
1. As judged by the investigator, any evidence of diseases (such as severe or
uncontrolled systemic diseases, including active bleeding diseases, psychiatric
illness/social situations), history of allogenic organ transplant, and/or substance
abuse which, in the investigator's opinion, makes it undesirable for the participant
to participate in the study or that would jeopardise compliance with the protocol.
2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to
swallow the formulated product, or previous significant bowel resection that would
preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
3. History of another primary malignancy.
4. Spinal cord compression and unstable brain metastases.
5. Clinically significant corneal disease.
6. Has active or uncontrolled hepatitis B or C virus infection.
7. Known HIV infection that is not well controlled.
8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals;
suspected infections (eg, prodromal symptoms); or inability to rule out infections
(participants with localised fungal infections of skin or nails are eligible).
9. Resting ECG with clinically abnormal findings.
10. Uncontrolled or significant cardiac disease.
11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
steroid treatment, or any evidence of clinically active ILD.
12. Has severe pulmonary function compromise.
Prior/Concomitant Therapy
13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent
targeting topoisomerase I, TROP2-targeted therapy.
Prior/Concurrent Clinical Study Experience
14. Participants with a known history of severe hypersensitivity reactions to either
Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with
a similar chemical structure or class to DXd and osimertinib.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Site
Address:
City:
Clayton
Zip:
3168
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Kogarah
Zip:
2217
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Westmead
Zip:
2145
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Barretos
Zip:
14784-400
Country:
Brazil
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Natal
Zip:
59075-740
Country:
Brazil
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Porto Alegre
Zip:
91350-200
Country:
Brazil
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Salvador
Zip:
41253-190
Country:
Brazil
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Sao Paulo
Zip:
01246-000
Country:
Brazil
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Montreal
Zip:
H4A 3J1
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Changchun
Zip:
130000
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Changsha
Zip:
410013
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Chengdu
Zip:
610000
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Chengdu
Zip:
610042
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Chongqing
Zip:
400030
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Guangzhou
Zip:
510100
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hangzhou
Zip:
310006
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hangzhou
Zip:
31000
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hankou,Wuhan
Zip:
430022
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Jinan
Zip:
250021
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Jinan
Zip:
250117
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Kunming
Zip:
650118
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Linhai
Zip:
318000
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Ningbo
Zip:
315010
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Shanghai
Zip:
200030
Country:
China
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Shenyang
Zip:
110004
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Xi'an
Zip:
710061
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Xuzhou
Zip:
221000
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Zhengzhou
Zip:
450008
Country:
China
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Berlin
Zip:
13125
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Erfurt
Zip:
99089
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Frankfurt
Zip:
60488
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Immenhausen
Zip:
34376
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Kiel
Zip:
24105
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Köln
Zip:
51109
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Mainz
Zip:
55131
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
München
Zip:
81925
Country:
Germany
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hong Kong
Zip:
999077
Country:
Hong Kong
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Lai Chi Kok
Country:
Hong Kong
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Monza
Zip:
20900
Country:
Italy
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Parma
Zip:
43100
Country:
Italy
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Chuo-ku
Zip:
104-0045
Country:
Japan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Fukuoka-shi
Zip:
812-8582
Country:
Japan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Yokohama-shi
Zip:
241-8515
Country:
Japan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Seoul
Zip:
120-752
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Seoul
Zip:
13620
Country:
Korea, Republic of
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Bystra
Zip:
43-360
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Olsztyn
Zip:
10-357
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Poznań
Zip:
60-569
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Warszawa
Zip:
02-781
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Barcelona
Zip:
8036
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Granada
Zip:
18007
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
La Coruña
Zip:
15006
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Majadahonda
Zip:
28222
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Valencia
Zip:
46009
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Taichung
Zip:
40705
Country:
Taiwan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Tainan
Zip:
704
Country:
Taiwan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Taipei City
Zip:
106
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Taipei
Zip:
10002
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Taipei
Zip:
TAIWAN
Country:
Taiwan
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Taoyuan
Zip:
333
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Bangkok
Zip:
10400
Country:
Thailand
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Bangkok
Zip:
10700
Country:
Thailand
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Dusit
Zip:
10300
Country:
Thailand
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Hat Yai
Zip:
90110
Country:
Thailand
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Mueang Udon Thani
Zip:
41000
Country:
Thailand
Status:
Not yet recruiting
Start date:
April 29, 2024
Completion date:
May 25, 2032
Lead sponsor:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Daiichi Sankyo
Agency class:
Industry
Source:
AstraZeneca
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06350097
