TALETRECTINIB for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Age ≥18 years (or ≥20 years as required by local regulations)\n- Patient with a life expectancy ≥12 weeks based on the judgment of investigator.\n- 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.\n- 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.\n- The patient is willing and capable to give written informed consent.\n- The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests, and other procedures.\n- The patient is willing and capable to comply with study site’s COVID-19 policies.\n- 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) For full list of Inclusion criteria please see section 5.1 in Protocol 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)\n- Histologically or cytologically confirmed diagnosis of locally advanced (including inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC (cohorts 1-3, 5) or other solid tumors including NSCLC patients ineligible for other cohorts (cohort 4).\n- 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.\n- Sufficient tumor tissue is required for patients in Cohort 1 and for TKI-naïve patients in Cohort 5 perform confirmatory ROS1 fusion testing at the designated central laboratories. For patients in cohort 1 and for TKI-naïve patients in Cohort 5, 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 in cohorts 2-4 and patients in Cohort 5 that received prior treatment with TKI(s) having ROS1 activity.\n- 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). • 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.\n- 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 line of systemic chemotherapy for locally advanced or metastatic ROS1-positive SCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1 activity.\n- At least 1 measurable disease per RECIST 1.1 assessed by investigator.\n- Eastern Cooperative Oncology Group Performance Status: 0 or 1."}

Exclusion criteria

• {"criterion_text":"- 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.\n- 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.\n- Radiation outside the chest and brain <7 days prior to C1D1.\n- 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.\n- Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has 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.\n- Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.\n- History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post-radiation pneumonitis).\n- Any gastrointestinal disorders that may affect absorption of oral medications.\n- 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\n- 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.\n- Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of any grade, or QT interval corrected for heart rate byFredericia's formula (QTcF) >470 milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or medical history of long QT syndrome.\n- Pregnancy or lactation/breastfeeding.\n- Use of food or drugs that are known potent cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment.\n- Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment.\n- 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 endpoints

• {"endpoint_text":"- Confirmed ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by an independent radiology review committee (IRC) (Cohorts 1-2)","definition_or_measurement_approach":"Objective response rate (ORR) assessed per RECIST 1.1 by independent radiology review committee (IRC) for Cohorts 1-2."}

Secondary endpoints

• {"endpoint_text":"- Efficacy DOR according to RECIST 1.1 assessed by IRC (Cohorts 1-2)","definition_or_measurement_approach":"Duration of response (DOR) per RECIST 1.1 assessed by IRC for Cohorts 1-2."}
• {"endpoint_text":"- Efficacy PFS according to RECIST 1.1 assessed by IRC (Cohorts 1-2)","definition_or_measurement_approach":"Progression-free survival (PFS) per RECIST 1.1 assessed by IRC for Cohorts 1-2."}
• {"endpoint_text":"- Efficacy TTF according to RECIST 1.1 assessed by IRC (Cohorts 1-2)","definition_or_measurement_approach":"Time to treatment failure (TTF) per RECIST 1.1 assessed by IRC for Cohorts 1-2."}
• {"endpoint_text":"- Efficacy TTR according to RECIST 1.1 assessed by IRC (Cohorts 1-2)","definition_or_measurement_approach":"Time to response (TTR) per RECIST 1.1 assessed by IRC for Cohorts 1-2."}
• {"endpoint_text":"- Efficacy ORR, DOR, and PFS according to RECIST 1.1 assessed by investigators (Cohorts 1-2)","definition_or_measurement_approach":"ORR, DOR and PFS per RECIST 1.1 assessed by investigators for Cohorts 1-2."}
• {"endpoint_text":"- Efficacy Confirmed intracranial (IC)-ORR, IC-DOR, IC-PFS, and time to intracranial progression (TTiP) according to mRECIST 1.1 assessed by IRC (Cohorts 1-2)","definition_or_measurement_approach":"Intracranial endpoints per mRECIST 1.1 assessed by IRC for Cohorts 1-2 (IC-ORR, IC-DOR, IC-PFS, TTiP)."}
• {"endpoint_text":"- Efficacy OS (Cohorts 1-2)","definition_or_measurement_approach":"Overall survival (OS) for Cohorts 1-2."}

Methods

• Recruitment procedure document (K1_2024-516604-41_Recruitment procedure) referenced in CTIS
• Patient Flyer (country-specific versions)
• Patient Brochure (country-specific versions)
• Patient Poster (country-specific versions)
• Patient ID Card
• Patient Study Guide / Patient Study Guide_Red_San
• Informed Consent Guide and ICF patient-facing documents

France

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

429

Number Of Sites

10

Number Of Participants

34

Italy

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

433

Number Of Sites

6

Number Of Participants

26

Spain

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

434

Number Of Sites

10

Number Of Participants

36

Poland

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

435

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Anheart Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Operational CRO functions; sponsorDuties codes: [1,12,15,2,3,8]; includes: Pharmacovigilance and site payments, medical services, patient materials

Name

Syneos Health CZ s.r.o.

Responsibilities

CRO functions; sponsorDuties codes: [9]

Third parties

• {"country":"Czechia","full_name":"Syneos Health CZ s.r.o.","duties_or_roles":"sponsorDuties codes: [9]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [1,12,15,2,3,8]; value: Pharmacovigilance and site payments, medical services, patient materials","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH (Weil Am Rhein)","duties_or_roles":"sponsorDuties codes: [14,15]; value: Labeling","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH (Allschwil)","duties_or_roles":"sponsorDuties codes: [14,15]; value: Labeling","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"sponsorDuties codes: [15]; value: Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH (Rheinfelden (Baden))","duties_or_roles":"sponsorDuties codes: [14,15]; value: Labeling","organisation_type":"Pharmaceutical company"}

Co-sponsors

• Nuvation Bio Inc.