IRB Study Number 22-055
Status Recruiting
Phase Phase 2
Institute Taussig Cancer Institute
Description
Primary Objective
• To evaluate the efficacy of taletrectinib by the objective response rate (ORR) in the patients of advanced or metastatic ROS1 positive NSCLC
Secondary Objectives
To evaluate the efficacy by duration of response (DOR)
To evaluate the efficacy by progression-free survival (PFS)
To evaluate the efficacy by time to failure (TTF)
To evaluate the efficacy by time to response (TTR)
To evaluate the efficacy by overall survival (OS)
To evaluate the efficacy endpoints (ORR, DOR and PFS) assessed by investigators
To evaluate the intracranial efficacy of taletrectinib
Inclusion Criteria
Patient age ≥18 years (or ≥20 years as required by local regulations).
Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (cohorts 1-3) or other solid tumors (cohort 4).
Evidence of ROS1 fusion in tumor tissue determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or locally equivalent diagnostic laboratories. The molecular assays (ie RT-PCR, NGS) are highly recommended
Sufficient tumor tissue is required for performing confirmatory ROS1 fusion testing at the designated central laboratories. For patients in cohort 1, an archival tumor tissue specimen should be available and collected prior to enrollment. If archival tumor tissue is unavailable, then a fresh biopsy must be performed. For patients in cohort 2, a fresh biopsy for tumor tissue is highly recommended before enrollment even if the archival tumor tissue is available. For patients in cohorts 3 and 4, either an archival tumor tissue or a fresh tumor tissue must be available before enrollment.
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):
• Cohort 1: Systemic chemotherapy naïve or pretreated with one prior line of chemotherapy, but never treated with any ROS1 TKI;
• Cohort 2: Prior treatment with one ROS1 TKI (crizotinib or entrectinib) and disease progression. The subject could be either chemotherapy naïve or has received one line of platinum and/or pemetrexed-based chemotherapy for the locally advanced or metastatic NSCLC.
• Cohort 3: Prior treatment with ≤ 2 ROS1 TKIs and disease progression. The subject could be either chemotherapy naïve or has received ≤ 2 lines of platinum and/ or pemetrexed-based chemotherapy for the locally advanced or metastatic NSCLC.
• Cohort 4: Systemic chemotherapy naïve or pretreated with ≤ 2 prior lines of chemotherapy, but never treated with any ROS1 TKI. ROS1 positive solid tumor types other than NSCLC will be enrolled.
At least one measurable disease per RECIST 1.1 assessed by investigators.
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:
a) Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤ 3.0 × upper limit of normal (ULN) (or ≤ 5.0 × ULN, for patients with concurrent liver metastases);
b) Serum total bilirubin: ≤ 1.5 × ULN;
c) Absolute neutrophil count: ≥1,500/μL;
d) Platelet count: ≥100,000/μL;
e) Hemoglobin: ≥ 9.0 g/dL;
f) Serum creatinine ≤ 1.5 x ULN and estimated creatinine clearance (CLcr) ≥45 mL/min as calculated using the method standard for the institution (eg. Cockcroft - Gault Equation)
- 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;
Females without menses for at least one 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 90 days after the last dose of investigational drug. Usage of hormonotherapy for contraception should be recorded as well. For detailed guidance on pregnancy and effective contraception, please refer to Appendix 4: Contraceptive and Barrier Guidance
- For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days of initial administration. Female patients of non-childbearing potential must meet at least 1 of the following criteria:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure.
All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
The patient is willing and capable to give written informed consent.
The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
Willing to comply with study site’s COVID-19 policies
Exclusion Criteria
Treatment with other investigational agents 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 before study treatment.
Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 except for AEs not constituting a safety risk to the patient in the judgment of investigators.
Patients with spinal cord compression caused by tumor and/or cancerous meningitis.
History or evidence of interstitial fibrosis, interstitial lung disease or TKI-induced pneumonitis. (Excluding clinically insignificant or asymptomatic post-radiation 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), hepatitis C virus (HCV), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known human immunodeficiency virus (HIV) and 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 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.
Pregnancy or lactation.
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. (See section 6.8 for details)
Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment. (See section 6.8 for details)
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 judgement of the Investigator.
