A Single-Arm, Open-Label, Multi-center Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients With Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors

Including patients who meet these criteria:

• Patient age ≥18 years (or ≥20 years as required by local regulations).
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC or other solid tumors.
• Evidence of ROS1 fusion in tumor tissue determined by molecular assays as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or locally equivalent laboratories.
• Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously treated and controlled, are allowed; the use of seizure prophylaxis is allowed as long as patients are taking non enzyme inducing anti-epileptic drugs (non-EIAEDs). If corticosteroid treatment is required, it should be on stable or decreasing dose of ≤10 mg prednisone or equivalent. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment at least 14 days before enrollment and be clinically stable.
• The patient is either ROS1 TKI treatment naïve, or treated with prior ROS1 TKI(s).
• At least one extracranial measurable unirradiated lesion per RECIST 1.1 assessed by investigator.
• Eastern Cooperative Oncology Group Performance Status: 0 or 1.
• Patient with a life expectancy ≥12 weeks based on the judgement of investigators.
• Patients with adequate organ function meeting the following criteria:
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤3 × upper limit of normal (ULN) (or ≤5 × ULN, in case of liver abnormalities due to liver metastases)
  • Serum total bilirubin: ≤1.5 × ULN
  • Absolute neutrophil count: ≥1,500/μL
  • Platelet count: ≥100,000/μL
  • Hemoglobin: ≥ 9.0 g/dL
  • Serum creatinine: ≤1.5 × ULN
• Males and/or females who meet any of the following criteria:
  • 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;
  • For females be post-menopausal for at least one year prior to screening or be documented surgically sterilized. Women of childbearing potential (WOCBP) must agree to use two concurrent effective methods of contraception or agree with complete abstinence from sexual intercourse since the informed consent until 90 days after the last dose of investigational drug. Usage of hormonotherapy for contraception should be recorded as well.
• The patient is willing and capable to give written informed consent.
• For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days of initial administration.
• Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion Criteria:

• Investigational agent or anticancer therapy within 2 weeks (or 5 half-lives of the compound, whichever is longer) prior to study enrollment. In addition, no concurrent anticancer therapy is permitted.
• Previously treated with immuno-oncology (IO) including immune checkpoint inhibitors within 12 weeks before enrollment.
• Major surgery within 4 weeks prior to enrollment.
• Radiation therapy with a limited field for palliation within 1 week of the first dose of study treatment.
• Toxicities due to prior therapy are unresolved to ≤ CTCAE 5.0 Grade 1 except for AEs not constituting a safety risk to the patient based on the judgment of investigators.
• Patients with spinal cord compression caused by tumor and/or cancerous meningitis.
• History or evidence of interstitial fibrosis or interstitial lung disease or pneumonitis.
• Any gastrointestinal disorders that may affect absorption of oral medications.
• Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Clinically significant cardiovascular diseases within 3 months prior to the first dose of investigational drug: myocardial infarction, severe/unstable angina, coronary/peripheral endovascular treatment, heart failure or cerebrovascular disorder including transient ischemic attack.
• Ongoing cardiac dysrhythmias of ≥ CTCAE 5.0 Grade 2, uncontrolled atrial fibrillation of any grade, or QT interval corrected for heart rate (QTc) interval >470 milliseconds (female) or QTc interval >450 milliseconds (male), or symptomatic bradycardia <45 beats per minute.
• Pregnancy or lactation.
• Patients with other severe medical or mental diseases in whom the risk is increased by the participation to the study or treatment with investigational drug in the opinion of the investigator.