A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

Locally Advanced or Metastatic Non-Small Cell Lung Cancer Clinical Trial

Official title:

An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05048797
• Other study ID #: D967SC00001
• Secondary ID: 2021-000634-33
• Status: Recruiting
• Phase: Phase 3
• Start date: October 28, 2021
• Est. completion date: March 29, 2027

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

DESTINY-Lung04 will investigate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) versus Standard of Care (SoC) as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) with HER2 Exon 19 or 20 mutations

Description:

Eligible participants will be those diagnosed with unresectable, locally advanced or metastatic histologically documented non-squamous NSCLC with HER2 exons 19 or 20 mutations and who are treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease. The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan as first-line treatment of Non-Small Cell Lung Cancer (NSCLC) as compared with Standard of Care treatment (Investigator's choice of cisplatin or carboplatin + pembrolizumab + pemetrexed). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse or simply to live longer, compared to patients receiving standard of care treatment. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: March 29, 2027
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 123 Years

Eligibility

Inclusion Criteria:

• Participants at least 18 years of age
• Locally advanced and unresectable NSCLC, not amenable to curative therapy, or metastatic disease
• Histologically documented non-squamous NSCLC with HER2 mutation in exons 19 or 20 by tissue NGS or ctDNA
• Treatment-naïve for palliative intent systemic therapy for locally advanced or metastatic disease
• Left ventricular ejection fraction (LVEF) = 50%
• Measurable disease assessed by Investigator based on RECIST 1.1
• Protocol-defined adequate organ function including cardiac, renal, hepatic function
• ECOG 0-1
• Having tumour tissue available for central testing

Exclusion Criteria:

• Tumors with targetable alterations to EGFR (or other targetable mutations including but not limited to ALK, if routinely tested as a targetable alteration with approved available therapy)
• Any untreated brain metastases, including asymptomatic or clinically inactive brain metastases
• Active autoimmune or inflammatory disorders
• Medical history of myocardial infarction within 6 months prior to randomization
• History of non-infectious pneumonitis/ILD, current or suspected ILD
• Lung-specific intercurrent clinical significant severe illness
• Contraindication to platinum-based doublet chemotherapy or pembrolizumab

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Trastuzumab Deruxtecan
Trastuzumab Deruxtecan administered by intravenous infusion
• Cisplatin
Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion
• Carboplatin
Investigator's choice of platinum chemotherapy (carboplatin) administered by intravenous infusion
• Pembrolizumab
Pembrolizumab administered by intravenous infusion
• Pemetrexed
Pemetrexed administered by intravenous infusion

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Rankweil
Austria	Research Site	Wien
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Leuven
Brazil	Research Site	Barretos
Brazil	Research Site	Blumenau
Brazil	Research Site	Brasília
Brazil	Research Site	Florianópolis
Brazil	Research Site	Natal
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Uberlândia
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Jinan
China	Research Site	Kunming
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	ShenZhen
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Yangzhou
China	Research Site	Zhengzhou City
Denmark	Research Site	Vejle
France	Research Site	Bordeaux
France	Research Site	Dijon
France	Research Site	Le Mans Cedex
France	Research Site	Lyon
France	Research Site	Marseille cedex
France	Research Site	Nantes
France	Research Site	Rennes Cedex 9
France	Research Site	Toulouse Cedex 9
France	Research Site	Villejuif Cedex
Germany	Research Site	Berlin-Zehlendorf
Germany	Research Site	Dresden
Germany	Research Site	Erfurt
Germany	Research Site	Heidelberg
Germany	Research Site	Immenhausen
Germany	Research Site	Köln
Germany	Research Site	Mainz
Germany	Research Site	Mannheim
Germany	Research Site	München
Germany	Research Site	Oldenburg
Germany	Research Site	Ravensburg
Germany	Research Site	Würzburg
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Jordan
Hong Kong	Research Site	Shatin
India	Research Site	Bangalore
India	Research Site	Delhi
India	Research Site	Hyderabad
India	Research Site	Mumbai
India	Research Site	Nashik
Italy	Research Site	Milan
Italy	Research Site	Monza
Italy	Research Site	Orbassano
Italy	Research Site	Parma
Italy	Research Site	Roma
Italy	Research Site	Verona
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yonago-shi
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Cdmx
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara Jalisco
Mexico	Research Site	Merida
Mexico	Research Site	Mexico City
Mexico	Research Site	Oaxaca
Mexico	Research Site	San Luis Potosí
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Groningen
Netherlands	Research Site	Leiden
Netherlands	Research Site	Nijmegen
Poland	Research Site	Bystra
Poland	Research Site	Gdansk
Poland	Research Site	Olsztyn
Poland	Research Site	Przemysl
Poland	Research Site	Warszawa
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Çankaya
Turkey	Research Site	Edirne
Turkey	Research Site	Izmir
Turkey	Research Site	Kadikoy/Istanbul
United States	Research Site	Anchorage	Alaska
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Basking Ridge	New Jersey
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Canton	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Commack	New York
United States	Research Site	Dallas	Texas
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Harrison	New York
United States	Research Site	Kennewick	Washington
United States	Research Site	La Crosse	Wisconsin
United States	Research Site	Los Alamitos	California
United States	Research Site	Los Angeles	California
United States	Research Site	Middletown	New Jersey
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Montvale	New Jersey
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	San Francisco	California
United States	Research Site	Santa Monica	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)	Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.	Until progression or death, assessed up to approximately 12 months
Secondary	Overall Survival (OS)	Defined as time from randomization until the date of death due to any cause.	Until death, assessed up to approximately 28 months.
Secondary	Progression Free Survival (PFS) by investigator assessment	Defined as time from randomization until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause.	Until progression, assessed up to approximately 12 months
Secondary	Objective Response Rate (ORR)	Defined as the proportion of participants who have a complete response (CR) or partial response (PR) as assessed by Blinded Independent Central Review (BICR) and investigator according to RECIST 1.1	Until progression, assessed up to approximately 12 months
Secondary	Duration of Response (DoR)	Defined as the time from the date of first documented response until date of documented progression as assessed by Blinded Independent Central Review (BICR) and investigator assessment according to RECIST 1.1.	Until progression, assessed up to approximately 12 months
Secondary	Time to second progression or death (PFS2)	Defined as the time from randomization until second progression on next-line of treatment as assessed by investigator at the local site using assessments conducted per local standard clinical practice, or death due to any cause.	Assessed up to approximately 20 months
Secondary	Landmark analysis of PFS (PFS12)	Defined as proportion of participants alive and progression-free at 12 months, as assessed by Blinded Independent Central Review (BICR) and investigator.	Assessed up to approximately 12 months
Secondary	Landmark analysis of OS (OS24)	Defined as proportion of participants alive at 24 months	Assessed up to approximately 24 months
Secondary	Central Nervous System (CNS) - Progression Free Survival (PFS)	Defined as time from randomization until Central Nervous System (CNS) progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR) or death due to any cause in the absence of CNS progression.	Until CNS progression or death, assessed up to approximately 12 months
Secondary	Safety and tolerability of T-DXd versus Standard of Care treatment	Assessed by the occurrence of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, ECG, and ECHO/MUGA scan results.	Until progression or death, assessed up to approximately 28 months
Secondary	Pharmacokinetics (PK) of T-DXd, total anti-HER2 antibody and DXd in serum	Serum concentration of T-DXd, total anti-HER2 antibody and DXd.	Up to cycle 4, approximately 12 weeks
Secondary	Immunogenicity of T-DXd	Presence of anti-drug antibodies (ADAs) for T-DXd.	Until progression, assessed up to approximately 13 months
Secondary	Patient-reported pulmonary symptoms associated with Non-Small Cell Lung Cancer	Time to sustained deterioration in pulmonary symptoms (cough, dyspnea, chest pain) while on treatment using the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ).	Until progression, assessed up to approximately 13 months
Secondary	Patient-reported tolerability of T-DXd described using symptomatic AEs	Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by the Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library.	Until progression, assessed up to approximately 13 months
Secondary	Patient-reported tolerability of T-DXd described using overall side-effect bother	Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the Patient's Global Impression of Treatment Tolerability (PGI-TT) while on treatment.	Until progression, assessed up to approximately 13 months
Secondary	Patient-reported tolerability of T-DXd described using physical function	Physical Function: The proportion of participants with maintained or improved physical function while on treatment, based on the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC-QLQ-C30) physical functioning scale.	Until progression, assessed up to approximately 13 months