Authorised Therapeutic exploratory (Phase II) Non-small Cell Lung Cancer

Taletrectinib in ROS1 Positive Lung Cancer Phase 2 Global Study

EU CTIS ID: 2024-516604-41-00

What this study is testing

For cohorts 1 to 5: To evaluate the efficacy of taletrectinib by the objective response rate (ORR) in the patients with advanced or metastatic ROS1 positive NSCLC For cohort 6: - Primary PK: To evaluate PK profile of taletrectinib at 400 mg QD when taken with a meal - Primary Safety: To evaluate the safety and tolerability of taletrectinib at 400 mg QD when taken with a meal

  • Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Age ≥18 years (or ≥20 years as required by local regulations)
  • Patient with a life expectancy ≥12 weeks based on the judgment of investigator.
  • 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) 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 2 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. Usage of hormonotherapy for contraception should be recorded as well.
  • For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days before starting study treatment. 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.

You likely can't join if

  • 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; or treatment with monoclonal antibodies including immune checkpoint inhibitors, within 4 weeks before the first dose of taletrectinib.
  • 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.
  • 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.
  • Pregnancy or lactation/breastfeeding.
  • Use of food or drugs that are known strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment (see Section 6.9.5 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 6.9.5 and 10.4 for details).
See the full eligibility criteria
Who can join
  • Age ≥18 years (or ≥20 years as required by local regulations)
  • Patient with a life expectancy ≥12 weeks based on the judgment of investigator.
  • 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) 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 2 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. Usage of hormonotherapy for contraception should be recorded as well.
  • For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days before starting study treatment. 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.
  • The patient is willing and capable to comply with study site’s COVID-19 policies.
  • 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 (≤3.0×ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy) c) Absolute neutrophil count: ≥1,500/μL d) Platelet count: ≥100,000/μL e) Hemoglobin: ≥9.0 g/dL f) Serum creatinine ≤1.5×ULN and estimated creatinine clearance (CLcr) ≥45 mL/min as calculated using the method standard for the institution (e.g., Cockcroft - Gault Equation)
  • Histologically or cytologically confirmed diagnosis of locally advanced (including inoperable Stage III NSCLC) or metastatic NSCLC (cohorts 1-3, 5, and 6) or other solid tumors including NSCLC patients ineligible for other cohorts (cohort 4).
  • Evidence of ROS1 fusion by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or locally equivalent diagnostic laboratories. The molecular assays (i.e., Reverse Transcription Polymerase Chain Reaction [RT-PCR], Next-generation Sequencing [NGS]) are highly recommended.
  • Sufficient tumor tissue is required for patients in Cohort 1 and for TKI-naïve patients in Cohort 5 and Cohort 6 to perform confirmatory ROS1 fusion testing at the designated central laboratories. For patients in Cohort 1 and for TKI-naïve patients in Cohort 5 and Cohort 6, 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. Tumor tissue for patients in other cohorts is highly recommended and tumor tissue obtained after progression on the most recent prior ROS1 TKI therapy in these cohorts is preferred. Cytology samples (e.g., pleural effusion cell pellets) may be acceptable for patients that received prior treatment with TKI(s) having ROS1 activity in Cohorts 2 to 6.
  • Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is stable (either asymptomatic or previously treated and controlled), are allowed: • Seizure prophylaxis is permitted with non-enzyme inducing antiepileptic drugs (non-EIAEDs; refer to Table 6-5 for examples of prohibited EIAEDs). • Corticosteroid treatment at a stable or decreasing dose within 7 days prior to the first dose of taletrectinib. • Whole brain radiation (WBRT) must be completed at least 14 days and stereotactic radiotherapy, stereotactic radiosurgery, or gamma knife radiotherapy at least 7 days prior to enrollment; the patient must be clinically stable for 7 days according to investigator judgement prior to first dose of taletrectinib.
  • The patient is either ROS1 TKI treatment naïve, or treated with prior ROS1 TKI(s): • Cohort 1: Patients with locally advanced or metastatic ROS1-positive NSCLC. Systemic chemotherapy naïve or pretreated with 1 prior line of chemotherapy but never treated with any ROS1 TKI. • Cohort 2: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior treatment with 1 approved ROS1 TKI (crizotinib or entrectinib) and disease progression. The patient can be either chemotherapy naïve or has received 1 line of systemic chemotherapy for the locally advanced or metastatic ROS1-positive NSCLC. • Cohort 3: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior treatment with ≥2 TKIs with ROS1 activity and disease progression. The patient can be either chemotherapy naïve or has received 1 line of systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC, patients with known ROS1 resistant mutations are preferred. • Cohort 4: Patients with other ROS1-positive solid tumors, or NSCLC patients ineligible for Cohorts 1-3. Prior treatment with ≤3 TKIs with ROS1 activity. The patient can be either chemotherapy naïve or has received ≤ 2 lines of systemic chemotherapy for locally advanced or metastatic solid tumors. • Cohort 5: Patients with locally advanced or metastatic ROS1-positive NSCLC. The patient can be either chemotherapy naïve or has received ≤2 lines of systemic chemotherapy for locally advanced or metastatic ROS1-positive SCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1 activity. • Cohort 6a: Patients with locally advanced or metastatic ROS1-positive NSCLC. Systemic chemotherapy naïve or pretreated with 1 prior line of chemotherapy but never treated with any ROS1 TKI. For Cohort 6a and 6b Inclusion criteria please see section 5.1 in Protocol
  • At least 1 measurable disease per RECIST 1.1 assessed by investigator.
  • Eastern Cooperative Oncology Group Performance Status: 0 or 1.
What rules you out
  • 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; or treatment with monoclonal antibodies including immune checkpoint inhibitors, within 4 weeks before the first dose of taletrectinib.
  • 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.
  • 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.
  • Pregnancy or lactation/breastfeeding.
  • Use of food or drugs that are known strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment (see Section 6.9.5 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 6.9.5 and 10.4 for details).
  • Patients with other severe medical or mental diseases in whom the risk is increased by the participation in the study or treatment with study treatment in the opinion of the Investigator.
  • Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib or anticipation of need for major surgical procedure during the study. • Placement of vascular access device is not considered major surgery. Other minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
  • Radiation outside the chest and brain <7 days prior to C1D1.
  • 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 initial diagnosis of the other malignancy. Note: This criterion does not apply to patients to be enrolled in Cohort 4.
  • Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or have not returned to baseline, at the time of the first dose of taletrectinib except for AEs not constituting a safety risk to the patient based on the judgment of investigators.
  • Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
  • History or evidence of interstitial fibrosis, interstitial lung disease, or drug-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) or acquired immunodeficiency syndrome (AIDS)-related illness. Note that the following are permitted: • Patients treated for hepatitis C (HCV) or HIV with no detectable viral load; for at least 1 month prior to the first dose of taletrectinib. Note: caution with drug-drug interactions of concomitant anti-HIV agents and CYP3A substrates. • Patients with known hepatitis B (HBV) infections: - With past or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of hepatitis B surface antigen [HBsAg]); or - With inactive HBV carrier state (defined as HBsAg-positive, with normal ALT, and HBV DNA <2,000 IU/mL or <10,000 copies/mL). Note: Please consider that for patients in an inactive HBV carrier state or with a resolved HBV infection, there may be a risk of HBV reactivation and anti-HBV prophylaxis should be considered

The study team makes the final eligibility decision.

Where it's taking place

  • United States
  • China
  • Korea, Republic of
  • Canada
  • Japan

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; China; Korea, Republic of; Canada; Japan. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.