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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04686305




Registration number
NCT04686305
Ethics application status
Date submitted
8/12/2020
Date registered
28/12/2020

Titles & IDs
Public title
Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC
Scientific title
A Phase Ib Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Immunotherapy Agents With and Without Chemotherapy Agents in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 (HER2) Overexpression (OE) (DESTINY-Lung03)
Secondary ID [1] 0 0
2020-003260-31
Secondary ID [2] 0 0
D967YC00001
Universal Trial Number (UTN)
Trial acronym
DL03
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - T-DXd
Treatment: Other - Durvalumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Volrustomig
Treatment: Drugs - Rilvegostomig

Experimental: Arm 1A: T-DXd, Durvalumab and Cisplatin - T-DXd, Durvalumab and Cisplatin

Experimental: Arm 1B: T-DXd, Durvalumab and Carboplatin - T-DXd, Durvalumab and Carboplatin

Experimental: Arm 1C: T-DXd, Durvalumab and Pemetrexed - T-DXd, Durvalumab and Pemetrexed (Arm not initiated)

Experimental: Arm 1D: T-DXd - T-DXd

Experimental: Arm 3A: T-DXd and Volrustomig - Drug: T-DXd and Volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig

Experimental: Arm 3B: T-DXd, Volrustomig and Carboplatin - Drug: T-DXd, Volrustomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig Drug: Carboplatin Carboplatin: administered as an IV infusion

Experimental: Arm 4A: T-DXd and Rilvegostomig - T-DXd and Rilvegostomig Drug: T-DXd, Rilvegostomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936

Experimental: Arm 4B T-DXd and Rilvegostomig with Carboplatin - Drug: T-DXd, Rilvegostomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936 Drug: Carboplatin Carboplatin: administered as an IV infusion


Treatment: Drugs: T-DXd
T-DXd: administered as an IV infusion

Treatment: Other: Durvalumab
Durvalumab: administered as an IV infusion

Treatment: Drugs: Cisplatin
Cisplatin: administered as an IV infusion

Treatment: Drugs: Carboplatin
Carboplatin: administered as an IV infusion

Treatment: Drugs: Pemetrexed
Pemetrexed: administered as an IV infusion (drug not used)

Treatment: Drugs: Volrustomig
Volrustomig: administered as an IV infusion

Treatment: Drugs: Rilvegostomig
Rilvegostomig: administered as an IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Frequency of AEs and SAEs
Timepoint [1] 0 0
Safety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent
Secondary outcome [1] 0 0
Confirmed Objective Response Rate (ORR)
Timepoint [1] 0 0
An average of approximately 12 months
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
An average of approximately 20 months
Secondary outcome [3] 0 0
Disease Control Rate (DCR)
Timepoint [3] 0 0
An average of approximately 12 months
Secondary outcome [4] 0 0
Progression-free survival (PFS)
Timepoint [4] 0 0
An average of approximately 20 months
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
An average of approximately 20 months
Secondary outcome [6] 0 0
Pharmacokinetics (PK) assessed by the serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181 in all arms
Timepoint [6] 0 0
An average of approximately 20 months
Secondary outcome [7] 0 0
Pharmacokinetics (PK) assessed by the serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
Timepoint [7] 0 0
An average of approximately 20 months
Secondary outcome [8] 0 0
Pharmacokinetics (PK) assessed by the serum concentration of volrustomig in study arms including T-DXd in combination with volrustomig
Timepoint [8] 0 0
An average of approximately 20 months
Secondary outcome [9] 0 0
Pharmacokinetics (PK) assessed by the serum concentration of rilvegostomig in study arms including T-DXd in combination with rilvegostomig
Timepoint [9] 0 0
An average of approximately 20 months
Secondary outcome [10] 0 0
The immunogenicity of T-DXd, durvalumab, volrustomig and rilvegostomig assessed by the presence of ADAs for T-DXd, durvalumab, volrustomig, or rilvegostomig
Timepoint [10] 0 0
An average of approximately 20 months

Eligibility
Key inclusion criteria
Inclusion criteria:

* Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
* Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
* Part 3 and 4: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed.
* Part 3 and 4: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred > 6 months from end of last therapy
* HER2overexpression status as determined by central review of tumor tissue
* WHO / ECOG performance status of 0 or 1
* Measurable target disease assessed by the investigator using RECIST 1.1
* Has protocol defined adequate organ and bone marrow function
* Part 3 and part 4: Minimum body weight of 35 kg.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* HER2 mutation if previously known
* Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
* Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen [HBsAg+ve] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC
* Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* 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
* Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke
* For Part 3 and Part 4: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class > II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
* Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
* For Part 3 and Part 4: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Unresolved toxicities not yet resolved to Grade = 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
* must not have any medical contraindication to platinum-based chemotherapy.
* Part 3 and 4 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.
* For Part 3 and Part 4: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
* For Part 3 and Part 4: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/12/2025
Actual
Sample size
Target
244
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Heidelberg
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Belgium
State/province [9] 0 0
Edegem
Country [10] 0 0
Canada
State/province [10] 0 0
Manitoba
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
France
State/province [13] 0 0
Bordeaux Cedex
Country [14] 0 0
France
State/province [14] 0 0
Dijon
Country [15] 0 0
France
State/province [15] 0 0
Pierre Benite Cedex
Country [16] 0 0
France
State/province [16] 0 0
Saint Herblain
Country [17] 0 0
France
State/province [17] 0 0
Villejuif Cedex
Country [18] 0 0
Israel
State/province [18] 0 0
Kfar-Saba
Country [19] 0 0
Israel
State/province [19] 0 0
Tel Hashomer
Country [20] 0 0
Italy
State/province [20] 0 0
Milano
Country [21] 0 0
Italy
State/province [21] 0 0
Monza
Country [22] 0 0
Italy
State/province [22] 0 0
Napoli
Country [23] 0 0
Italy
State/province [23] 0 0
Padova
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Cheongju-si
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Goyang-si
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Jinju-si
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Malaysia
State/province [28] 0 0
George Town
Country [29] 0 0
Malaysia
State/province [29] 0 0
Kuala Lumpur
Country [30] 0 0
Malaysia
State/province [30] 0 0
Kuching
Country [31] 0 0
Malaysia
State/province [31] 0 0
Selangor
Country [32] 0 0
Netherlands
State/province [32] 0 0
Amsterdam
Country [33] 0 0
Philippines
State/province [33] 0 0
Bacolod
Country [34] 0 0
Philippines
State/province [34] 0 0
Cebu City
Country [35] 0 0
Philippines
State/province [35] 0 0
Davao City
Country [36] 0 0
Philippines
State/province [36] 0 0
Manila
Country [37] 0 0
Philippines
State/province [37] 0 0
Quezon City
Country [38] 0 0
Philippines
State/province [38] 0 0
San Juan
Country [39] 0 0
Philippines
State/province [39] 0 0
Taguig City
Country [40] 0 0
Poland
State/province [40] 0 0
Gdansk
Country [41] 0 0
Poland
State/province [41] 0 0
Kraków
Country [42] 0 0
Poland
State/province [42] 0 0
Olsztyn
Country [43] 0 0
Poland
State/province [43] 0 0
Tomaszów Mazowiecki
Country [44] 0 0
Poland
State/province [44] 0 0
Warszawa
Country [45] 0 0
Singapore
State/province [45] 0 0
Singapore
Country [46] 0 0
Spain
State/province [46] 0 0
Badalona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Sevilla
Country [49] 0 0
Spain
State/province [49] 0 0
Valencia
Country [50] 0 0
Taiwan
State/province [50] 0 0
Kaohsiung city
Country [51] 0 0
Taiwan
State/province [51] 0 0
Taichung City
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taichung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Tainan
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taoyuan
Country [56] 0 0
Thailand
State/province [56] 0 0
Bangkok
Country [57] 0 0
Thailand
State/province [57] 0 0
Hat Yai
Country [58] 0 0
Thailand
State/province [58] 0 0
Khon Kaen
Country [59] 0 0
Thailand
State/province [59] 0 0
Muang
Country [60] 0 0
Turkey
State/province [60] 0 0
Ankara
Country [61] 0 0
Turkey
State/province [61] 0 0
Bornova-Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04686305