Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Single-arm trial whereby all consented, enrolled, eligible patients receive taletrectinib

Taletrectinib

Lian Li

Misako Nagasaka, MD

The main purpose of the study is to evaluate safety and efficacy of taletrectinib (also known as AB-106 or DS-6051b) monotherapy in the treatment of advanced NSCLC.

This is a global Phase 2, multicenter, single-arm, open label study of taletrectinib in patients of NSCLC harboring with ROS1 fusion gene.

About 224 patients will be enrolled and divided into 6 cohorts, depending on past history of ROS1 TKI treatment.

In the cohorts open to enrollment, taletrectinib will be administered either 400mg or 600mg once daily in 21-day cycles. In one cohort, this will be in combination with carboplatin and pemetrexed both administered by IV infusion in 21-day cycles for 4 cycles. Patients will continue with the treatment on taletrectinib until progression of disease as determined by the investigator.

The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow up will be conducted as well.

Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC

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

Confirmed IC-PFS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria

Confirmed ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by an independent radiology review committee (IRC)

PFS according to RECIST 1.1 assessed by IRC

ORR according to RECIST 1.1 assessed by investigators

Incidence of Adverse events (AEs), incidence of laboratory abnormalities, incidence of abnormal vital signs, abnormal ECG and abnormal ophthalmologic findings

Maximum Plasma Concentration (Cmax) of taletrectinib

AnHeart Therapeutics Inc.

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Chlorotrianisene

Crizotinib

Taletrectinib 600mg will be given po daily every day within 2 hours of meals on days 1-21, on a 21-day cycle. Study drug will be given until intolerance, consent withdrawal, progression per RECIST 1.1, or death (i.e., no maximum number of cycles).

Taletrectinib (AB-106/DS-6051b) is a potent, highly selective, orally bioavailable ROS1 and TRK family inhibitor, which has activity against mutations conferring resistance to crizotinib including in vitro and in vivo against the acquired ROS1 G2032R solvent front mutation. Taletrectinib has been shown to have anti-tumor activity against recombinant ROS1, NTRK1, and NTRK3 in sub-nanomolar concentration in an ATP dependent manner, in addition to completely inhibiting ACK, ALK, DDR1 and LTK at micromolar concentrations. Anti-tumor activity of taletrectinib was observed in two ROS1 rearranged lung cancer cell lines, glioblastoma cell line, and in NTRK-rearranged colorectal cancer cell lines.

Megan Kruse, MD

Zeina Nahleh, MD

Megan Kruse

The purpose of this study is to evaluate the safety and tolerability of talectrectinib as treatment for Stage IV ILC with CDH1 mutation

Invasive lobular cancer (ILC) represents 10-15% of all breast cancers, up to 75% of ILCs carry a mutation in CDH1 gene which encodes for e-cadherin (ECAD), which is a cell adhesion glycoprotein. Preclinical data using patient derived xenografts have shown loss of ECAD due to CDH1 mutation is associated with an upregulation ROS1 activity, and ROS1 inhibitors have demonstrated synthetic lethality in CDH1-mutated cell lines. Taletrectinib is a novel ROS1/NTRK inhibitor with demonstrated activity in ROS1 mutated non-small cell lung cancer. The purpose of the trial is to estimate the activity of taletrectinib in previously treated CDH1-mutated metastatic breast ILC.

Single arm, prospective phase II study of taletrectinib in participants with CDH1-mutated breast metastatic ILC

Taletrectinib in Previously Treated Metastatic CDH1-mutated Invasive Lobular Cancer (ILC)

A Phase II Study of Taletrectinib in Previously Treated Metastatic CDH1-mutated Invasive Lobular Cancer (ILC) of the Breast (TaCe)

All participant data will be shared via peer-reviewed publication as a combined summary. Any individual outcomes published per subject will be deidentified utilizing the subject ID (eg. Dose level, demographics, adverse events etc.)

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence.

Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Clinical benefit rate as measured by total number of participants with complete response, partial response and stable disease in participants treated with taletrectinib

Defined as the subset of participants who achieved a confirmed CR or PR from the date of first documentation of objective response (CR or PR) to the date of first documentation of progressive disease (PD).

Incidence tables will be generated to summarize incidence of participants reporting at least one episode of each specific adverse event, incidence of adverse events causing withdrawals and incidence of serious adverse events. Listing of adverse events by participants will include the time to onset, the duration of each event, the severity of each event, and the relationship of the event to study therapy, whether it was a serious event, and whether it caused withdrawal. Proportion and exact confidence boundaries (95% CI) will be estimated for toxicity.

The EORTC QLQ-C30 questionnaire is a 30-item cancer-specific questionnaire that incorporates 5 functioning scales (physical, role, cognition, emotional, and social), 8 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, loss of appetite, constipation, diarrhea), financial well-being scale and a global scale (based on 2 items: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?").

The FACT-B v4.0 is a 37-item self-reported instrument designed for participants to report on quality of life measures within 5 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Breast Cancer Subscale.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC	NCT04919811	Non Small Cell ...	Taletrectinib	18 Years -	AnHeart Therapeutics Inc.
Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC	NCT04919811	Non Small Cell ...	Taletrectinib	18 Years -	AnHeart Therapeutics Inc.
Taletrectinib in Previously Treated Metastatic CDH1-mutated Invasive Lobular Cancer (ILC)	NCT06214793	Breast Cancer Metastatic Brea...	Taletrectinib	18 Years -	Case Comprehensive Cancer Center

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