Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)
- Registration Number
- NCT04484142
- Lead Sponsor
- Daiichi Sankyo
- Brief 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.
- Detailed 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 137
Participants eligible for inclusion in the study must meet all inclusion criteria for this study.
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Sign and date the inform consent form (ICF) prior to the start of any study- specific qualification procedures.
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Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)
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Has pathologically documented NSCLC that:
- Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
- 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.
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Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
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Participant must meet the following for advanced or metastatic NSCLC:
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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.
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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).
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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.
-
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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.
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Measurable disease based on local imaging assessment using RECIST v1.1.
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Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.
Participants meeting any exclusion criteria for this study will be excluded from this study.
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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.
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Has leptomeningeal carcinomatosis.
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Has prior treatment with:
- Any chemotherapeutic agent targeting topoisomerase I, including antibody drug conjugate (ADC) containing such agent.
- TROP2-targeted therapy.
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Uncontrolled or significant cardiovascular disease:
- History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
- History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
- 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.
- History of serious cardiac arrhythmia requiring treatment.
- LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.
- Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).
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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.
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Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
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Clinically significant corneal disease.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DS-1062a 6.0 mg/kg DS-1062a Participants will receive 6.0 mg/kg of DS-1062a
- Primary Outcome Measures
Name Time Method Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months. 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From baseline up to approximately 24 months Progression-free Survival (PFS) From baseline up to approximately 24 months Pharmacokinetic Parameter Maximum Concentration (Cmax) From baseline up to approximately 24 months Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) From baseline up to approximately 24 months Percentage of Participants Who Reported Treatment-emergent Adverse Events (TEAE) From baseline up to approximately 24 months Overall Survival (OS) From baseline up to approximately 24 months Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) From baseline up to approximately 24 months
Trial Locations
- Locations (82)
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Sarah Cannon Research Institute at Florida Cancer Center, South
🇺🇸Port Charlotte, Florida, United States
UCLA
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
The Netherlands Cancer Institute
🇳🇱Amsterdam, North Holland, Netherlands
University of Michigan
🇺🇸Detroit, Michigan, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Osaka City General Hospital
🇯🇵Osaka-shi, Osaka, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Osaka, Japan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Shizuoka Cancer Center
🇯🇵Nagaizumi-chō, Shizuoka, Japan
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Kyoto University Hospital
🇯🇵Kyoto-shi, Kyoto, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Niigata, Japan
NYU Langone Medical Center
🇺🇸New York, New York, United States
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Kansai Medical University Hospital
🇯🇵Hirakata-shi, Osaka, Japan
National Taiwan University Hospital NTUH
🇨🇳Taipei, Taiwan
Tokushima University Hospital
🇯🇵Tokushima-shi, Tokushima, Japan
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
The Office of Dr. Frederick P. Smith MD
🇺🇸Chevy Chase, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
XCancer / Regional Cancer Care Associate (Astera)
🇺🇸East Brunswick, New Jersey, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
New York Cancer and Blood Specialists
🇺🇸Port Jefferson, New York, United States
Avera Cancer Institute Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Virginia Cancer Specialists
🇺🇸Athens, Virginia, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
University Hospital of Nantes
🇫🇷Nantes, Loire-Atlantique, France
APHM - Hopital Nord
🇫🇷Marseille Cedex 20, Bouches-Du-Rhône, France
Gustav Roussy Cancer Campus Grand Paris
🇫🇷Villejuif, ile-de-France, France
CHU Toulouse Hopital Larrey
🇫🇷Toulouse, Occitanie, France
Centre Leon Berard
🇫🇷Lyon, Rhone, France
CHU Louis Pradel
🇫🇷Lyon, France
Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil
🇫🇷Strasbourg, France
Institut Curie
🇫🇷Paris, France
Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse
🇫🇷Toulon, France
Thoraxklinik Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Asklepios Fachklinik Muenchen-Gauting
🇩🇪Gauting, Bayern, Germany
IKF Krankenhaus Nordwest
🇩🇪Frankfurt Am Main, Hessen, Germany
Azienda Ospedaliera Universitaria Policlinico-OVE
🇮🇹Catania, CT, Italy
Universitaet zu Koeln - Uniklinik Koeln
🇩🇪Koeln, North Rhine-Westphal, Germany
National Koranyi Institute for TB and Pulmonology
🇭🇺Budapest, Hungary
Pulmonology Hospital Törökbálint
🇭🇺Torokbalint, Hungary
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, RM, Italy
University of Turin San Luigi Hospital
🇮🇹Orbassano, Torino, Italy
Azienda Ospedaliero-Universitaria S. Orsola Malpighi
🇮🇹Bologna, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Ospedaliera Arcispedale Santa Maria
🇮🇹Reggio Emilia, Italy
Fujita Health University Hospital
🇯🇵Toyoake-shi, Aichi, Japan
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
Hokkaido Cancer Center
🇯🇵Sapporo-shi, Hokkaido, Japan
Kindai University Hospital
🇯🇵Ōsaka-sayama, Osaka, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Tokyo, Japan
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam, Gyeonggi-do, Korea, Republic of
Hospital Universitario Puerta de Hierro de Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Regional Universitario Malaga
🇪🇸Málaga, Malaga, Spain
Erasmus MC
🇳🇱Rotterdam, Zuid Holland, Netherlands
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Vall dHebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Sarah Cannon Research Institute at Florida Cancer Center, North
🇺🇸Gainesville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States