Clinical trial NCT04484142: Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Metastatic Non-small Cell Lung Cancer
Advanced Metastatic Non-small Cell Lung Cancer
Non-small Cell Lung Cancer
DS-1062a
Datopotamab Deruxtecan
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2020-07-23
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR)
timeFrame: From baseline until disease progression, death, or other protocol defined reason, up to approximately 24 months.
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From baseline up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: From baseline up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: From baseline up to approximately 24 months
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax)
timeFrame: From baseline up to approximately 24 months
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
timeFrame: From baseline up to approximately 24 months
measure: Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)
timeFrame: From baseline up to approximately 24 months
measure: Percentage of Participants Who Reported Treatment-emergent Adverse Events (TEAE)
timeFrame: From baseline up to approximately 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Gainesville
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Center, North
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Port Charlotte
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Center, South
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chevy Chase
country: United States
facility: The Office of Dr. Frederick P. Smith MD
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: East Brunswick
country: United States
facility: XCancer / Regional Cancer Care Associate (Astera)
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Port Jefferson
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Sioux Falls
country: United States
facility: Avera Cancer Institute Sioux Falls
state: South Dakota
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Athens
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Marseille Cedex 20
country: France
facility: APHM - Hopital Nord
state: Bouches-Du-RhÃ´ne
city: Villejuif
country: France
facility: Gustav Roussy Cancer Campus Grand Paris
state: ile-de-France
city: Nantes
country: France
facility: University Hospital of Nantes
state: Loire-Atlantique
city: Toulouse
country: France
facility: CHU Toulouse Hopital Larrey
state: Occitanie
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone
city: Lyon
country: France
facility: CHU Louis Pradel
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg- Nouvel Hopital Civil
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal Toulon La Seyne sur mer Hopital Sainte-Musse
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
state: Baden-Württemberg
city: Gauting
country: Germany
facility: Asklepios Fachklinik Muenchen-Gauting
state: Bayern
city: Frankfurt Am Main
country: Germany
facility: IKF Krankenhaus Nordwest
state: Hessen
city: Koeln
country: Germany
facility: Universitaet zu Koeln - Uniklinik Koeln
state: North Rhine-Westphal
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Budapest
country: Hungary
facility: National Koranyi Institute for TB and Pulmonology
city: Torokbalint
country: Hungary
facility: Pulmonology Hospital Törökbálint
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico-OVE
state: CT
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: RM
city: Orbassano
country: Italy
facility: University of Turin San Luigi Hospital
state: Torino
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S. Orsola Malpighi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Reggio Emilia
country: Italy
facility: Azienda Ospedaliera Arcispedale Santa Maria
city: Toyoake-shi
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo-shi
country: Japan
facility: Hokkaido Cancer Center
state: Hokkaido
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital
state: Kyoto
city: Niigata-shi
country: Japan
facility: Niigata Cancer Center Hospital
state: Niigata
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka City General Hospital
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Nagaizumi-chō
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Tokushima-shi
country: Japan
facility: Tokushima University Hospital
state: Tokushima
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
state: North Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid Holland
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
state: Madrid
city: Málaga
country: Spain
facility: Hospital Regional Universitario Malaga
state: Malaga
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Vall dHebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital NTUH
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: