Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC
- Registration Number
- NCT04919811
- Lead Sponsor
- Nuvation Bio Inc.
- Brief Summary
The main purpose of the study is to evaluate safety and efficacy of taletrectinib (also known as AB-106 or DS-6051b) monotherapy in the treatment of advanced NSCLC.
- Detailed Description
This is a global Phase 2, multicenter, single-arm, open label study of taletrectinib in patients of NSCLC harboring with ROS1 fusion gene.
About 224 patients will be enrolled and divided into 6 cohorts, depending on past history of ROS1 TKI treatment.
In the cohorts open to enrollment, taletrectinib will be administered either 400mg or 600mg once daily in 21-day cycles. In one cohort, this will be in combination with carboplatin and pemetrexed both administered by IV infusion in 21-day cycles for 4 cycles. Patients will continue with the treatment on taletrectinib until progression of disease as determined by the investigator.
The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow up will be conducted as well.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 224
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Age ≥18 years (or ≥20 years as required by local regulations).
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Histologically or cytologically confirmed diagnosis of locally advanced (including inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC or other solid tumors.
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Evidence of ROS1 fusion by a validated assay.
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Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, must be stable, either asymptomatic or previously treated and controlled within 14 days of first dose.
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The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s).
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The patient must have at least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
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Eastern Cooperative Oncology Group Performance Status: 0 or 1.
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Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
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Patients with adequate organ function meeting the following criteria:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver metastases)
- Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy)
- Absolute neutrophil count: ≥1,500/μL
- Platelet count: ≥100,000/μL
- Hemoglobin: ≥9.0 g/dL
- Serum creatinine ≤1.5 × ULN
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Patients must be able to practice required contraception during the study.
- For males (irrespective of surgical sterilization [vasectomy]): agree to use effective contraception methods during the study intervention period and for at least 90 days after the last dose of investigational drug or agree with complete abstinence.
- Females without menses for at least 1 year prior to screening or documented to be surgically sterilized. Women of childbearing potential (WOCBP) must agree to use two concurrent highly effective methods of contraception or agree with complete abstinence from sexual intercourse since the informed consent until 45 days after the last dose of investigational drug. The patient is willing and capable to give written informed consent.
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The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
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The patient is willing and capable to comply with study site's COVID-19 policies.
Exclusion Criteria
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Treatment with small molecule anticancer therapy including other investigational agents or cytotoxic systemic anticancer therapy within 2 weeks (or 5 half-lives of the compound, whichever is shorter) prior to the first dose of taletrectinib; Treatment with immuno-oncology (IO) including immune checkpoint inhibitors within 4 weeks before the first dose of taletrectinib.
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Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib.
• Placement of vascular access device is not considered major surgery. Other minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
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Radiotherapy within 14 days before study treatment. Stereotactic radiosurgery (SRS), stereotactic radiation therapy (SRT), and palliative radiation outside the chest and brain are allowed but must be completed 1 week before starting study treatment.
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Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
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Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has not returned to baseline, by the first dose of taletrectinib except for AEs not constituting a safety risk to the patient based on the judgment of investigators.
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Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
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History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis.
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Any gastrointestinal disorders that may affect absorption of oral medications.
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Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
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Clinically significant cardiovascular diseases within 3 months prior to the first dose of taletrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral endovascular treatment, heart failure or cerebrovascular disorder including transient ischemic attack.
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Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) >470 milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or medical history of long QT syndrome.
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Pregnancy or lactation/breastfeeding.
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Use of food or drugs that are known potent cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers or P-glycoprotein inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment.
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Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment.
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Patients with other severe medical or mental diseases in whom the risk is increased by the participation to the study or treatment with study treatment in the opinion of the investigator.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Taletrectinib Taletrectinib Single-arm trial whereby all consented, enrolled, eligible patients receive taletrectinib
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) by independent radiology review committee (IRC) Up to 4 years Confirmed ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by an independent radiology review committee (IRC)
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to 4 years PFS according to RECIST 1.1 assessed by IRC
Objective response rate (ORR) assessed by investigators Up to 4 years ORR according to RECIST 1.1 assessed by investigators
Safety and tolerability of taletrectinib Up to 4 years Incidence of Adverse events (AEs), incidence of laboratory abnormalities, incidence of abnormal vital signs, abnormal ECG and abnormal ophthalmologic findings
Pharmacokinetic (PK) profile of taletrectinib Up to 4 years Maximum Plasma Concentration (Cmax) of taletrectinib
Trial Locations
- Locations (73)
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Renovatio Clinical
🇺🇸Dallas, Texas, United States
Texas Oncology, P.A.
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Moores Cancer Center at UC San Diego
🇺🇸La Jolla, California, United States
Keck Medicine of University of Southern California
🇺🇸Los Angeles, California, United States
UCI Medical Center
🇺🇸Orange, California, United States
PMK Medical Group Inc
🇺🇸Oxnard, California, United States
American Institute of Research
🇺🇸Whittier, California, United States
SCRI - Florida Cancer Specialists South
🇺🇸Fort Meyers, Florida, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
SCRI - Hematology Oncology Clinic
🇺🇸Baton Rouge, Louisiana, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Center for Cancer Research
🇺🇸Brick, New Jersey, United States
Renovatio Clinical - The Woodlands
🇺🇸Houston, Texas, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre Research Institute
🇨🇦Montréal, Quebec, Canada
Hunan Cancer Hospital
🇨🇳Changsha, China
West China Hospital
🇨🇳Chengdu, China
Shandong Cancer Hospital
🇨🇳Jinan, China
Wuhan Union Hospital
🇨🇳Wuhan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
🇫🇷Bron, France
CHU de Grenoble - Hôpital Albert Michallon
🇫🇷Grenoble, France
Centre Léon Bérard
🇫🇷Lyon, France
Hôpital Nord - CHU Marseille
🇫🇷Marseille, France
ICO - Site René Gauducheau
🇫🇷Nantes, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
CHU Poitiers - Hopital la Miletrie
🇫🇷Poitiers, France
Godinot Cancer Institute
🇫🇷Reims, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico
🇮🇹Bari, Italy
Humanitas Istituto Clinico Catanese, Misterbinanoco
🇮🇹Catania, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
AOU Cagliari- P.O. Policlinico Universitario Duilio Casula
🇮🇹Monserrato, Italy
Azienda Ospedaliera Universitaria- Università degli Studi della Campania
🇮🇹Napoli, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
Sendai Kousei Hospital
🇯🇵Miyagi, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷Gyeongsang, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Med-Polonia Sp. z o.o.
🇵🇱Poznań, Poland
MICS Centrum Medyczne Toruńa
🇵🇱Toruń, Poland
Instytut Centrum Zdrowia Matki Polki
🇵🇱Łódź, Poland
Clinica Mi Tres Torres
🇪🇸Barcelona, Spain
Hospital General de Catalunya
🇪🇸Barcelona, Spain
Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat
🇪🇸Barcelona, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Instituto Valenciano de Oncologia IVO
🇪🇸Valencia, Spain