Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)

Metastatic Non Small Cell Lung Cancer Clinical Trial

Official title:

A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05555732
• Other study ID #: DS1062-A-U303
• Secondary ID: 2022-500802-16-0
• Status: Recruiting
• Phase: Phase 3
• Start date: January 11, 2023
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 908-992-6400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

Description:

The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS <50% and advanced or metastatic NSCLC without actionable genomic alternations. Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 975
• Est. completion date: August 2027
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Sign and date the Main Informed Consent Form (ICF), prior to the start of any study- specific qualification procedures.
• Adults =18 at the time the Main ICF is signed.
• Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing.
• Has provided a formalin-fixed tumor tissue sample for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers.
• Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC.
• Has measurable disease based on local imaging assessment using RECIST v1.1.
• Histologically documented NSCLC that meets all of the following criteria:
• Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition).
• Documented negative test results for epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations based on analysis of tumor tissue.
• No known actionable genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), or other actionable driver kinases with locally approved therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
• Has an adequate treatment washout period before Cycle 1 Day 1.
• Is willing and able to participate in the collection of patient-reported outcomes (PRO) data.

Exclusion Criteria:

• Has received prior systemic treatment for advanced/metastatic NSCLC.
• Has received prior treatment with any of the following, including in the

adjuvant/neoadjuvant (for NSCLC) setting:

• Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
• TROP2-targeted therapy.
• Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti-PD-ligand 2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
• Any other immune checkpoint inhibitors.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
• Has spinal cord compression or clinically active untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Uncontrolled or significant cardiovascular disease, including:
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex.
• Myocardial infarction within 6 months prior to randomization.
• Uncontrolled angina pectoris within 6 months prior to randomization.
• LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
• New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
• Uncontrolled hypertension within 28 days before randomization.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
• History of another primary malignancy (beyond NSCLC) except for:
• Malignancy treated with curative intent and with no known active disease =3 years before the first dose of study treatment and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage =T2cN0M0 without biochemical recurrence or progression.
• Has a history of severe hypersensitivity reactions to either the drugs or inactive ingredients of Dato-DXd, pembrolizumab, carboplatin, cisplatin or pemetrexed.
• Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Has known human immunodeficiency virus (HIV) infection that is not well controlled.
• Has active or uncontrolled hepatitis B or C infection.
• Female who is pregnant or breastfeeding or intends to become pregnant.
• Any other medical conditions, including cardiac disease or psychological disorders, and/or substance abuse.
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has active, known, or suspected autoimmune disease.
• Has clinically significant corneal disease.
• Has had an allogeneic tissue/solid organ transplantation.
• Has received prior radiotherapy =4 weeks of start of study intervention or more than 30 Gy to the lung within 6 months of Cycle 1 Day 1.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non Small Cell Lung Cancer

Intervention

Drug:
• Datopotamab Deruxtecan
Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Pembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Pemetrexed
Pemetrexed will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Carboplatin
Carboplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
• Cisplatin
Cisplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Locations

Country	Name	City	State
Argentina	Fundacion CENIT para la investigacion en Neurociencias	Ciudad Autonoma de Buenos Aire
Argentina	Centro de Investigacion Pergamino Sa	Pergamino
Argentina	Sanatorio Parque	Rosario
Australia	CRSA/ St Andrews Hospital	Adelaide
Australia	Flinders Medical Centre (Fmc)	Bedford Park
Australia	PSEHOG (Peninsula and South Eastern Haematology and Oncology Group)	Frankston
Australia	Southern Medical Day Care Centre	Wollongong
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	Klinikum Klagenfurt Pulmologie	Klagenfurt
Belgium	Az Maria Middelares - Campus Maria Middelares	Gent
Belgium	Az Nikolaas	Sint-Niklaas
Brazil	Personal Oncologia de Precisao - Cenantron	Belo Horizonte
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui
Brazil	Clínica de Neoplasias Litoral Ltda	ItajaA-
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Centro de Estudos E Pesquisa de Hematologia E Oncologia - Cepho	Santo Andre
Brazil	Instituto de Ensino E Pesquisa Sao Lucas	Sao Paulo
Canada	CHU de Quebec -Universite Laval Hopital de L'Enfant-Jesus	Quebec City
Chile	Centro de Estudios Clinicos Saga Spa	Santiago de Chile
Chile	Centro de Investigaciones Clinicas Vina Del Mar	ViAaa Del Mar
China	Peking University Peoples Hospital	Beijing
China	Peking University Cancer Hospital Beijing Cancer Hospital Beijing Institute For Cancer Research	Beijing Sheng
China	Cangzhou Peoples Hospital	Cangzhou
China	First Affiliated Hospital of Medical College of Jilin University	Changchun
China	Jilin Cancer Hospital	Changchun
China	Hunan Cancer Hospital	Changsha
China	University of Electronic Science Technology of China UESTC - Sichuan Cancer Hospital Institute SIC	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
China	Fujian Medical University - Union Hospital Foochow Christian Union Hospital	Fuzhou
China	Affiliated Cancer Hospital and Insititute of Guangzhou Medical University	Guangzhou
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital of College of Medicine Zhejiang University	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	An Hui Cancer Hospital	Hefei
China	Inner Mongolia Medical University- the Affiliated Hospital	Hohhot
China	Jiamusi Cancer Hospital	Jiamusi
China	Linyi Cancer Hospital	Linyi
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Zhongda Hospital, Southeast University	Nanjing
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai Chest Hospital	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang
China	The First Affiliated Hosptial of Xinjiang Medical University	Ürümqi
China	Union Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	The First Affiliate Hospital of Xi'An Jiaotong University	Xi'an
China	Xiangyang Central Hospital	Xianyang
China	Henan Cancer Hospital	Zhengzhou
France	Chu de Bordeaux - Hopital Saint Andre	Bordeaux
France	Centre Hospitalier Universitaire, CHU, de Poitiers	France
France	Centre Leon Berard	Lyon
France	Aphm - Hopital Nord	Marseille Cedex 20
France	Hopital Prive Du Confluent	Nantes
France	Tenon Hospital	Paris
France	Hôpital Foch	Suresnes
Germany	Klinikum Esslingen Gmbh	Esslingen
Greece	Bioclinic Thessaloniki (Galinos Clinic)	Thessalonki
Hong Kong	Prince of Wales Hospital / The Chinese University of Hong Kong	Hong Kong
Hong Kong	Queen Mary Hospital	Pok Fu Lam
Hungary	Bkmk Hospital	KecskemAŠt
Hungary	Fejer Megyei Szent Gyorgy Korhaz Pulmonologiai Osztaly	Szekesfehervar
Italy	Ospedale S. Maria Della Misericordia	Udine
Italy	Asst Sette Laghi	Varese
Japan	Kurume University Hospital	Azuma
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo-Ku
Japan	Kyushu University Hospital	Fukuoka
Japan	Matsusaka Municipal Hospital	Hataji
Japan	Kansai Medical University Hospital	Hirakata
Japan	Iwakuni Clinical Center	Iwakuni
Japan	Kanazawa University Hospital	Kanazawa-shi
Japan	Juntendo University Hospital	Kanemaru
Japan	The Cancer Institute Hospital of JFCR	Koto
Japan	NHO Shikoku Cancer Center	Kozuki
Japan	Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc. Saiseikai Kumamoto Hospital	Kumamoto
Japan	University Hospital Kyoto Prefectual University of Medicine	Kyoto
Japan	Matsusaka City Hospital	Matsusaka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Kyushu Cancer Center	Okamato
Japan	Teine Keijinkai Hospital	Sapporo-shi
Japan	Sendai Kousei Hospital	Sendai
Japan	Dokkyo Medical University Hospital	Shimotsuga-gun
Japan	Osaka Toneyama Medical Center	Toyonaka-shi
Japan	Yamaguchi-Ube Medical Center	Ube-shi
Japan	Kanagawa Cancer Center	Yokohama
Korea, Republic of	Chungbuk National University Hospital	Cheongjusi
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Gangnam-Gu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si Gyeongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Netherlands	Jeroen Bosch Ziekenhuis Jbz	s-Hertogenbosch
Poland	Instytut Centrum Zdrowia Matki Polki (Iczmp)	Lodz
Romania	Onco Clinic Consult Sa	Craiova
Romania	Oncocenter Oncologie Clinica S.R.L	Timisoara
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Arnau de Vilanova	Lleida
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Regional Universitario Malaga	Malaga
Spain	CHUO	Ourense
Spain	Hosp Univ Virgen Macarena	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	China Medical University Hospital	Hsia
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Ramathibodi Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Chiang Mai University CMU - Maharaj Nakhon Chiang Mai Hospital Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Prince of Songkla University PSU - Faculty of Medicine	Hat Yai
Thailand	Khon Kaen University - Faculty of Medicine-Srinagarind Hospital	Mueang Nonthaburi
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	American Oncology Partners of Maryland	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute; Inv Drg Svc Pharm	Boston	Massachusetts
United States	North Shore Hematology Oncology Associates dba NY Cancer and Blood Specialists - Bronx	Bronx	New York
United States	Ironwood Cancer and Research Centers	Chandler	Arizona
United States	UCHealth Memorial Hospital	Colorado Springs	Colorado
United States	Maryland Oncology Heamtology P.A.	Columbia	Maryland
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Southern Cancer Center Pc	Daphne	Alabama
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Regional Cancer Care Associates LLC	Hackensack	New Jersey
United States	Cancer Specialist of North Florida	Jacksonville	Florida
United States	Providence Regional Cancer System	Lacey	Washington
United States	North Shore Hematology Oncology Associates dba NY Cancer and Blood Specialists- New Hyde Park	New Hyde Park	New York
United States	Hoag Memorial Hospital Prebyterian	Newport Beach	California
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Cancer Care Centers of Brevard, Inc.	Palm Bay	Florida
United States	North Shore Hematology Oncology Associates	Patchogue	New York
United States	Woodlands Medical Specialists, Pa	Pensacola	Florida
United States	North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists	Port Jefferson Station	New York
United States	Arizona Oncology Associates, Pc - Nahoa	Prescott Valley	Arizona
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Florida Cancer Specialists-North	Saint Petersburg	Florida
United States	Utah Cancer Specialists IHO Corp	Salt Lake City	Utah
United States	Ut Health San Antonio	San Antonio	Texas
United States	Sansum Clinic	Santa Barbara	California
United States	Texas Oncology-Tyler	Tyler	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Based on Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 29 months
Primary	Overall Survival in Participants in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Overall Survival (OS) is defined as the time from randomization to death due to any cause.	From randomization until disease progression or death (whichever occurs first), up to approximately 57 months
Secondary	Objective Response Rate by Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 29 months
Secondary	Progression-free Survival by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 29 months
Secondary	Objective Response Rate by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 29 months
Secondary	Duration of Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1.	From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 29 months
Secondary	Time to Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1.	From randomization to date of first objective response (CR or PR), up to approximately 29 months
Secondary	Disease Control Rate by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 29 months
Secondary	Progression-free Survival 2 in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Progression-free Survival 2 (PFS2) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by local standard clinical practice	From randomization until disease progression or death (whichever occurs first), up to approximately 57 months
Secondary	Time to Deterioration in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	Time to Deterioration (TTD) is defined as the time from randomization to first onset of a =10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent =10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a =10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13).	From randomization until disease progression or death (whichever occurs first), up to approximately 57 months
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAE) in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)	A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment.	Up to 57 months
Secondary	Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA	The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.	Baseline and up to 57 months