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

NCT06214793 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: CASE5123
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Breast Cancer; Metastatic Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) as measured by RECIST v1

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

  24 Weeks

Secondary Outcomes (6)

• Progression Free Survival Rate(PFS)

  Every 12 weeks until 180 days from EOT until death, withdrawal of informed consent, loss of follow-up or termination of the study by the sponsor, whichever occurs first.

• Clinical Benefit Rate

  Up to 6 months (180 days) after completion of therapy or until death, whichever comes first

• Duration Of Response(DOR)

  Up to 6 months (180 days) after completion of therapy or until death, whichever comes first

• Safety analysis, with toxicities graded according to NCI CTCAE v5.0

  Up to 30 days after the final dose of the study drug

• Overall Quality Of Life(QOL) with EORTC QLQ-C30 assessments

  Assessed every 12 weeks starting from first treatment visit till EOT and then every 12 weeks until 6 months after EOT

Study Arms (1)

Taletrectinib

EXPERIMENTAL

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).

Drug: Taletrectinib

Interventions

Taletrectinib DRUG

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.

Also known as: AB-106

Taletrectinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• History of histologically or cytologically confirmed diagnosis invasive lobular carcinoma and current diagnosis of metastatic breast cancer
• Presence of CDH1 mutation as confirmed by any commercially available next generation sequencing (NGS) testing on tumor tissue or liquid biopsy specimens
• Negative HER2 testing (IHC 1+ or 2+ with negative FISH)
• Prior Therapy requirements:
• For estrogen receptor positive (ER+) participants: prior endocrine therapy with a CDK4/6 inhibitor and at least 1 chemotherapy or antibody drug conjugate in the metastatic setting
• For estrogen receptor negative (ER-) participants: at least 2 prior lines of chemotherapy or antibody drug conjugate received in the metastatic setting
• Participants with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is stable (either asymptomatic or previously treated and controlled are allowed as follows:
• Seizure prophylaxis is permitted with non-enzyme-inducing anti-epileptic drugs (non- EIAEDs).
• Corticosteroid treatment at a stable or decreasing dose of ≤10 mg prednisone or equivalent if required within 7 days prior to the first dose of taletrectinib.
• Local therapy including but not limited to whole brain radiation or gamma knife irradiation treatment must be completed at least 14 days before enrollment and the participant clinically stable (e.g., no corticosteroids or anticonvulsant treatment) for 7 days prior to first dose of taletrectinib (for participants with neurological symptoms or signs due to CNS metastasis at screening).
• At least 1 measurable lesion per RECIST 1.1 assessed by investigator.
• Eastern Cooperative Oncology Group Performance Status: 0-2
• Participant with a life expectancy ≥12 weeks based on the judgement of investigator.
• Participant with adequate organ function meeting the following criteria:

You may not qualify 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; Treatment with immuno-oncology (IO) including immune checkpoint inhibitors within 4 weeks before the first dose of taletrectinib.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib.
• a) Placement of vascular access device is not considered major surgery. Other minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
• Radiotherapy within 14 days before study treatment. Stereotactic radiosurgery (SRS), stereotactic radiation therapy (SRT), and palliative radiation outside the chest and brain are allowed but must be completed 1 week before starting study treatment.
• Have been diagnosed with another primary malignancy except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• 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.
• Participants 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:
• Participants 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.
• Participants with known hepatitis B (HBV) infections:
• i. with past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of hepatitis B surface antigen \[HBsAg\]);

Sponsors & Collaborators

• Megan Kruse, MD: lead
• AnHeart Therapeutics Inc.: collaborator

Study Sites (2)

Marone Cancer Center Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

taletrectinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Megan Kruse

  Cleveland Clinic Foundation, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, MD

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

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 22, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer reviewed publication will be publicly available. No raw data will be shared
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. CCF personnel will not share study data apart from that which has been published publicly.

Locations

US (2)