Clinical trial NCT04919811: Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC
Official title: A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients with Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Nuvation Bio Inc.
Sponsor class: INDUSTRY
Collaborators: name: AnHeart Therapeutics Inc.
First posted: 2021-06-09
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years (or ≥20 years as required by local regulations).
2. Histologically or cytologically confirmed diagnosis of locally advanced (including inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC or other solid tumors.
3. Evidence of ROS1 fusion by a validated assay.
4. 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.
5. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s).
6. The patient must have at least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
7. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
8. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
9. Patients with adequate organ function meeting the following criteria:

   1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver metastases)
   2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy)
   3. Absolute neutrophil count: ≥1,500/μL
   4. Platelet count: ≥100,000/μL
   5. Hemoglobin: ≥9.0 g/dL
   6. Serum creatinine ≤1.5 × ULN
10. Patients must be able to practice required contraception during the study.

    1. 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.
    2. 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.
11. The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
12. The patient is willing and capable to comply with study site's COVID-19 policies.

Exclusion Criteria

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
7. History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis.
8. Any gastrointestinal disorders that may affect absorption of oral medications.
9. 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.
10. 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.
11. 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.
12. Pregnancy or lactation/breastfeeding.
13. 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.
14. Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment.
15. 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.

Primary outcomes:
measure: Objective response rate (ORR) by independent radiology review committee (IRC)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 4 years
measure: Objective response rate (ORR) assessed by investigators
timeFrame: Up to 4 years
measure: Safety and tolerability of taletrectinib
timeFrame: Up to 4 years
measure: Pharmacokinetic (PK) profile of taletrectinib
timeFrame: Up to 4 years
Other outcomes:
measure: Intracranial progression-free survival (IC-PFS)
timeFrame: Up to 4 years
measure: Intracranial objective response rate (IC-ORR)
timeFrame: Up to 4 years
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego
state: California
city: Los Angeles
country: United States
facility: Keck Medicine of University of Southern California
state: California
city: Orange
country: United States
facility: UCI Medical Center
state: California
city: Oxnard
country: United States
facility: PMK Medical Group Inc
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Fort Meyers
country: United States
facility: SCRI - Florida Cancer Specialists South
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Baton Rouge
country: United States
facility: SCRI - Hematology Oncology Clinic
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Brick
country: United States
facility: Center for Cancer Research
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Renovatio Clinical
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Renovatio Clinical - The Woodlands
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre Research Institute
state: Quebec
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Bron
country: France
facility: CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Nantes
country: France
facility: ICO - Site René Gauducheau
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Poitiers
country: France
facility: CHU Poitiers - Hopital la Miletrie
city: Reims
country: France
facility: Godinot Cancer Institute
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico
city: Catania
country: Italy
facility: Humanitas Istituto Clinico Catanese, Misterbinanoco
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Monserrato
country: Italy
facility: AOU Cagliari- P.O. Policlinico Universitario Duilio Casula
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria- Università degli Studi della Campania
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Gyeongsang
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Toruńa
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Barcelona
country: Spain
facility: Clinica Mi Tres Torres
city: Barcelona
country: Spain
facility: Hospital General de Catalunya
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia IVO
Study officials:
affiliation: AnHeart Therapeutics Inc.
name: Lian Li
role: STUDY_DIRECTOR
References: