TRUST-II

JRCT ID: jRCT2071210051

Registered date:13/08/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: ROS1 positive advanced or metastatic non-small cell lung cancer (NSCLC) and Other Solid Tumors
• Date of first enrollment: 31/08/2021
• Target sample size: 20
• Countries of recruitment: United States,Japan,Canada,Japan,France,Japan,Italy,Japan,Spain,Japan,korea,Japan
• Study type: Interventional
• Intervention(s): AB-106 600 mg orally administered once daily every day. Dose reduction by 1st level, or if needed by 2nd level, will be allowed depending on the type and severity of toxicity encountered.

Outcome(s)

• Primary Outcome: To evaluate the efficacy of AB-106 by the objective response rate (ORR)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patient age 18 years and over (or 20 years and over as required by local regulations).
2. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic
NSCLC (cohorts 1-3) or other solid tumors (cohort 4).
3. Evidence of ROS1 fusion in tumor tissue determined by molecular assays as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or locally equivalent laboratories. Sufficient tumor tissue is required for performing confirmatory ROS1 fusion testing at the designated central laboratories.
4. Patients in cohort 1 must have an archival tumor tissue specimen available and collected prior to enrollment. If archival tumor tissue is unavailable, then a mandatory fresh biopsy must be performed. For patients in cohort 2, a mandatory fresh biopsy is required before enrollment even if archival tumor tissue is available. For cohorts 3-4, either an archival tumor tissue or a fresh tumor sample must be available before enrollment.
5. 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 equivalent or less. 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.
6. The patient is either ROS1 TKI treatment naive, or treated with prior ROS1 TKI(s):
Cohort 1: Systemic chemotherapy naive or pretreated with one prior line of chemotherapy, but never treated with any ROS1 TKI
Cohort 2: Pretreated with one prior ROS1 TKI which is locally marketed, AND pretreated with <=1 prior line of chemotherapy
Cohort 3: Pretreated with >=2 prior ROS1 TKIs, AND pretreated with <=2 prior lines of chemotherapy
Cohort 4: Systemic chemotherapy naive or pretreated with <=2 prior lines of chemotherapy, but never treated with any ROS1 TKI.
7. At least one extracranial measurable unirradiated lesion per RECIST 1.1 assessed by investigators.
8. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
9. Patient with a life expectancy 12 weeks based or more on the judgement of investigators.
10. Patients with adequate organ function meeting the following criteria:
a) AST and ALT: <=3 x upper limit of normal (ULN) (or <=5 x ULN, in case of liver abnormalities due to liver
metastases)
b) Serum total bilirubin: <=1.5 x ULN
c) Absolute neutrophil count: >=1,500 per microliter
d) Platelet count: >=100,000 per microliter
e) Hemoglobin: >=9.0 g per deciliter
f) Serum creatinine: <=1.5 x ULN.
11. Males and/or females who meet any of the following criteria:
a) 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;
b) 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.
12. The patient is willing and capable to give written informed consent.
13. For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days of initial administration.
14. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclude criteria

1. 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.
2. Previously treated with immuno-oncology (IO) including immune checkpoint inhibitors within 12 weeks before enrollment.
3. Major surgery within 4 weeks prior to enrollment.
4. Radiation therapy with a limited field for palliation within 1 week of the first dose of study treatment.
5. 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.
6. Patients with spinal cord compression caused by tumor and/or cancerous meningitis.
7. History or evidence of interstitial fibrosis or interstitial lung disease or 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) or hepatitis C virus (HCV), 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
investigational drug: myocardial infarction, severe/unstable angina,coronary/peripheral
endovascular treatment, heart failure or cerebrovascular disorder including transient ischemic attack.
11. 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.
12. Pregnancy or lactation.
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.
14. 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.

Related Information

• Primary Sponsor: Nakayama Tomoko