Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Non-small Cell Lung Cancer Clinical Trial

Official title:

Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum Based Chemotherapy (TROPION-Lung05)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04484142
• Other study ID #: DS1062-A-U202
• Secondary ID: 2020-002774-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 30, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

Description:

This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC with actionable genomic alterations and who have been previously been treated with 1 platinum-containing therapy and 1 or more lines of targeted therapy. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all participants either have been followed for at least 9 months after the start of study treatment or have discontinued from the study, whichever occurs first.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 137
• Est. completion date: December 31, 2024
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria for this study.

• Sign and date the inform consent form (ICF) prior to the start of any study- specific qualification procedures.

• Adults =18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)

• Has pathologically documented NSCLC that:

1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).

2. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.

KRAS mutations in the absence of any of the genomic alterations specified above will be excluded.

Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for enrollment.

Participants who have not received osimertinib should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase inhibitor (TKI), unless the participant is already known to be positive with document results for this mutation or unless osimertinib is not locally approved.

• Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.

• Participant must meet the following for advanced or metastatic NSCLC:

1. Has been treated with at least one but no more than two cytotoxic agent-containing therapy in the metastatic setting:

• One platinum-containing regimen (either as monotherapy or combination therapy).

• May have received up to one additional line of cytotoxic agent-containing therapy.

• Those who received a platinum-containing regimen as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.

2. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent).

3. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally approved for the participant's applicable genomic alteration at the time of screening:

• Those who received a targeted agent for the applicable genomic alterations in the study as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alterations (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.

• Participants who have been treated with a prior TKI must receive additional targeted therapy, if clinically appropriate, for the genomic alterations that are considered amenable or the participant will not be allowed in the study.

• Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the mandatory biopsy collected during screening.

• Measurable disease based on local imaging assessment using RECIST v1.1.

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study.

• Has 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. Participants with clinically inactive brain metastases may be included in the study.

• Has leptomeningeal carcinomatosis.

• Has prior treatment with:

1. Any chemotherapeutic agent targeting topoisomerase I, including antibody drug conjugate (ADC) containing such agent.

2. TROP2-targeted therapy.

• Uncontrolled or significant cardiovascular disease:

1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.

2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.

3. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening. Participants with a history of Class II to IV CHF prior to screening must have returned to Class I CHF and have LVEF =50% (by either an ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.

4. History of serious cardiac arrhythmia requiring treatment.

5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.

6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).

• 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.

• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses

• Clinically significant corneal disease.

• Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for =3 years.

Related Conditions & MeSH terms

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

Intervention

Drug:
• DS-1062a
DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon	Rhone
France	CHU Louis Pradel	Lyon
France	APHM - Hopital Nord	Marseille Cedex 20	Bouches-Du-Rhône
France	University Hospital of Nantes	Nantes	Loire-Atlantique
France	Institut Curie	Paris
France	Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil	Strasbourg
France	Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse	Toulon
France	CHU Toulouse Hopital Larrey	Toulouse	Occitanie
France	Gustav Roussy Cancer Campus Grand Paris	Villejuif	ile-de-France
Germany	IKF Krankenhaus Nordwest	Frankfurt Am Main	Hessen
Germany	Asklepios Fachklinik Muenchen-Gauting	Gauting	Bayern
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Thoraxklinik Heidelberg	Heidelberg	Baden-Württemberg
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Universitaet zu Koeln - Uniklinik Koeln	Koeln	North Rhine-Westphal
Hungary	National Koranyi Institute for TB and Pulmonology	Budapest
Hungary	Pulmonology Hospital Törökbálint	Torokbalint
Italy	Azienda Ospedaliero-Universitaria S. Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria Policlinico-OVE	Catania	CT
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	University of Turin San Luigi Hospital	Orbassano	Torino
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Azienda Ospedaliera Arcispedale Santa Maria	Reggio Emilia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	RM
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	Kansai Medical University Hospital	Hirakata-shi	Osaka
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo
Japan	Kyoto University Hospital	Kyoto-shi	Kyoto
Japan	Shizuoka Cancer Center	Nagaizumi-cho	Shizuoka
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Kindai University Hospital	Osaka-sayama	Osaka
Japan	Osaka City General Hospital	Osaka-shi	Osaka
Japan	Osaka International Cancer Institute	Osaka-shi	Osaka
Japan	Hokkaido Cancer Center	Sapporo-shi	Hokkaido
Japan	Tokushima University Hospital	Tokushima-shi	Tokushima
Japan	Fujita Health University Hospital	Toyoake-shi	Aichi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Netherlands	The Netherlands Cancer Institute	Amsterdam	North Holland
Netherlands	Erasmus MC	Rotterdam	Zuid Holland
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Vall dHebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario Malaga	Málaga	Malaga
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital NTUH	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United States	Virginia Cancer Specialists	Athens	Virginia
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	The Office of Dr. Frederick P. Smith MD	Chevy Chase	Maryland
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Michigan	Detroit	Michigan
United States	XCancer / Regional Cancer Care Associate (Astera)	East Brunswick	New Jersey
United States	Sarah Cannon Research Institute at Florida Cancer Center, North	Gainesville	Florida
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	University of California San Diego	La Jolla	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	NYU Langone Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	AdventHealth Orlando	Orlando	Florida
United States	Mayo Clinic	Phoenix	Arizona
United States	Sarah Cannon Research Institute at Florida Cancer Center, South	Port Charlotte	Florida
United States	New York Cancer and Blood Specialists	Port Jefferson	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCLA	Santa Monica	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Avera Cancer Institute Sioux Falls	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca

Countries where clinical trial is conducted

United States,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)	ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months.
Secondary	Duration of Response (DOR)		From baseline up to approximately 24 months
Secondary	Progression-free Survival (PFS)		From baseline up to approximately 24 months
Secondary	Overall Survival (OS)		From baseline up to approximately 24 months
Secondary	Pharmacokinetic Parameter Maximum Concentration (Cmax)		From baseline up to approximately 24 months
Secondary	Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)		From baseline up to approximately 24 months
Secondary	Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)		From baseline up to approximately 24 months
Secondary	Percentage of Participants Who Reported Treatment-emergent Adverse Events (TEAE)		From baseline up to approximately 24 months