Adult Disease, Adult Solid Tumor, Advanced Solid Tumor, Cancer, EGFR, KRAS G12C, NSCLC, Squamous Cell Lung Cancer
Conditions
Keywords
TOLREMO, Drug resistance, TT125-802, Small molecule, Bromodomain inhibitor, NSCLC
Brief summary
The purpose of this study is to test the safety and therapeutic effect of TT125-802 (single agent) in subjects with advanced solid tumors.
Detailed description
The purpose of this Phase 1, First-in-Human, Open-label Study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of TT125-802 as single agent in subjects with advanced solid tumors.
Interventions
DRUGTT125-802
TT125-802 administered orally
Sponsors
TOLREMO therapeutics AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and nonpregnant and non-breastfeeding females, aged ≥ 18 years of age at the time of signing the informed consent. * Subjects with advanced solid tumors resistant or refractory to standard treatment. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Measurable disease per RECIST 1.1 criteria. * Adequate hematological function defined by absolute neutrophil count, ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 9 g/dL, and without growth factor treatment or blood transfusion within 2 weeks before the study intervention start. * Adequate hepatic function defined by total bilirubin level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) level ≤ 3 × ULN, and an alanine aminotransferase (ALT) level ≤ 3 × ULN. * Adequate renal function defined by creatinine clearance \> 60 mL/min according to the Cockcroft-Gault equation or creatinine levels \<1.5 mg/dl. * Adequate coagulation laboratory assessments, as follows: Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN), or international normalized ratio (INR) \< 1.5 or within target range if on prophylactic anticoagulation therapy. * Life expectancy of \> 3 months, in the opinion of the Investigator. * Willing to adhere to contraception, egg and sperm donation, the fasting requirement, and other criteria as described in lifestyle restrictions * Capable of giving signed informed consent.
Exclusion criteria
* Clinically significant (i.e., active) uncontrolled intercurrent illness. * Presence of brain metastases unless clinically stable. * History or presence of malignancies unless curatively treated with no evidence of disease ≥ 2 years. * Subjects with known human immunodeficiency virus and/or active viral hepatitis (B and/or C), and subjects on viral hepatitis B therapy are excluded. However, subjects with hepatitis C treated with curative therapy are not considered actively infected. * Subject received a live vaccine within 30 days prior to the first dose of the study treatment administration. * Serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease, and/or other situation that may preclude adequate absorption of oral medications. * Subjects that have received a strong CYP3A4 inhibitor within 7 days prior to the first dose of TT125-802 or a strong CYP3A4 inducer within 14 days prior to the first dose of TT125-802. * Hypersensitivity to the active substance or to any of the excipients of TT125-802.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) | Day 1 to approximately 16 weeks |
| Frequency of dose interruptions and dose reductions | Day 1 to approximately 16 weeks |
| Incidence of dose-limiting toxicities (DLTs) | Day 1 to Day 21 |
| Recommended Dose(s) for Expansion | Day 1 to Day 21 |
Secondary
| Measure | Time frame |
|---|---|
| Plasma concentration of TT125-802 in blood | Day 1 to approximately 16 weeks |
| Objective response rate (ORR) assessed by RECIST v1.1 | Day 1 to approximately 16 weeks |
| Duration of response (DOR) according to RECIST v1.1 | Day 1 to approximately 16 weeks |
| Progression-free survival (PFS) according to RECIST v1.1 | Day 1 to approximately 16 weeks |
Countries
Spain, Switzerland, United States
Outcome results
None listed