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

Exclusion Criteria

• •1. 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.
• •2. 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.
• •3. 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.
• •4. 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.
• •5. 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.
• •6. Participants with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
• •7. History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post-radiation pneumonitis).
• •8. Any gastrointestinal disorders that may affect absorption of oral medications.
• •9. 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:
• •1. 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.
• •2. 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 \[HBsAg\]);
• •or
• •ii. 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 participants 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.
• •10. Clinically significant cardiovascular diseases within 3 months prior to the first dose of talectrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral endovascular treatment, heart failure or cerebrovascular disorder including transient ischemic attack.
• •11. 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.
• •12. Pregnancy or lactation/breastfeeding.
• •13. 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.
• •14. Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment.
• •15. Participants 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.