A Phase 1/2 Study of TAS3351 in Patients with Advanced Non-Small Cell Lung Cancer and EGFR Mutations
- Conditions
- Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation.MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- CTIS2022-502595-23-00
- Lead Sponsor
- Taiho Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 102
1. Provide written informed consent, 8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, 9. Adequate organ function as defined by the following criteria: a. Absolute neutrophil count (ANC) = 1.5 × 10^9/L b. Platelet count = 100,000/mm^3 (= 100 × 10^9/L); last transfusion of blood products must be =2 weeks prior to start of study treatment. c. Hemoglobin = 9.0 g/dL d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT = 5.0 × ULN e. Total bilirubin = 1.5 × ULN, or = 3.0 × ULN for patients with Gilbert’s syndrome f. Creatinine clearance (CrCl) (calculated or measured value): =50 mL/min. For calculated CrCl, use the Cockcroft-Gault formula g. Potassium blood levels =3.0 mmol/L, In addition to the above, patients in France must meet the following criterion: 12. Affiliated with a social security system or be a beneficiary of an equivalent system of patient care as applicable by local regulations in France., 10. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female patients are not considered to be of child-bearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy)., 11. Both males and females of reproductive potential must agree to use highly effective birth control throughout the study and at least for: - 6 months after the last dose of study treatment for females - 3 months after the last dose of study treatment for males or longer, based on local requirements, 2. =18 years of age (or meets the country’s regulatory definition for legal adult age, whichever is greater), 3. Histologically or cytologically confirmed, locally advanced, non-resectable or metastatic NSCLC, 4. Has received the following prior treatment and no more than 2 lines of prior cytotoxic chemotherapy for locally advanced or metastatic disease setting: a. Part A1 (Phase 1 Dose Escalation): Standard of care (SOC) that is available to the patient, unless contraindicated, intolerable to the patient, or declined by the patient b. Part A2: Progression on third-generation EGFR TKI (eg, osimertinib, lazertinib) and having received or not eligible for platinum-based chemotherapies or other targeted approved therapies in case of off-target alterations. c. Parts B and C: Progression on third-generation EGFR TKI (eg, osimertinib, lazertinib), 5. Has the following EGFRmt status as determined by a CLIA certified (US), locally certified (outside of the US), or the study central laboratory based on tumor tissue or plasma cfDNA: a. Part A1 (Phase 1 Dose Escalation): Any EGFRmt b. Parts A2, B, and C: Any sensitizing EGFRmt and a confirmed C797S EGFRmt (Note: no T790M EGFRmt required), 6. Has tumor tissue available collected after progression on the most recent systemic EGFR TKI treatment in a quantity sufficient to allow for analysis of EGFRmt status by the Sponsor’s central laboratory (optional for Part A1 only). Please refer to the Laboratory Manual for details., 7. Has measurable disease per RECIST v1.1 (optional for patients in Part A1)
1. Currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study, 8. Known hypersensitivity to the ingredients of TAS3351, 9. Unable to swallow whole tablets, 12. Vulnerable patients who are: a. Deprived of their liberty by a judicial or administrative decision. b. Receiving psychiatric care c. Admitted to a health or social institution for purposes other than research. d. Under legal protection (ie, guardianship, curatorship, and safeguard of justice) e. Unable to express their consent., 10. Pregnant female or breastfeeding female, 11. Any other clinically significant acute or chronic medical or psychiatric condition that may increase the risk associated with study drug administration, or may interfere with the interpretation of study results based on Investigator discretion, 2. Has received prior treatment with any of the following within the specific time frame prior to the first dose of study treatment: a. Major surgery/surgical therapy for any cause within 4 weeks; the patient must have recovered adequately from the toxicity and/or complications of the intervention prior to starting study treatment b. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, or investigational agents within 5 half-lives or within 4 weeks (whichever is shorter) prior to the first dose of study treatment. Patient must have recovered from toxicities of the prior therapy based on the Investigator’s judgement prior to starting study treatment c. No prior treatment with: (i). Part A1 (Phase 1 Dose Escalation): Systemic immunotherapy (eg, PD- 1/PD-L1 antibody) (ii). Parts A2, B, and C: Any EGFR C797S mutation-targeting agent (eg, BLU-945) d. Radiotherapy prior to the start of study treatment within: (i). 2 weeks for radiation therapy of non-thoracic regions (7 days for palliative radiation of single lesions) (ii). 3 months for radiation therapy including thoracic region. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis., 3. Have any unresolved clinically relevant toxicity of Grade = 2 from previous anti-cancer treatment, except for alopecia, skin pigmentation, and Grade 2, prior platinum-therapy related neuropathy. Patients with chronic, but stable Grade 2 toxicities may be allowed to enroll if the Investigator and Sponsor agree., 4. Any strong and moderate inhibitors/inducers of cytochrome P450 (CYP) 3A two weeks prior to start of therapy. If a patient is receiving strong inhibitors/inducers of CYP3A (see Appendix A), these medications and substances must be discontinued =2 weeks prior to the first dose of study treatment., 5. Has the following CNS metastases disease status: a. Part A1 (Phase 1 Dose Escalation): Known untreated central nervous system (CNS) metastases, or history of uncontrolled seizures, or leptomeningeal disease. b. Parts A2, B, and C: Spinal cord compression, symptomatic and unstable CNS metastases, requiring steroids over the last 4 weeks prior to enrollment., 6. Impaired cardiac function or clinically significant cardiac disease, including any of the following: a. Baseline QT interval > 470 msec (for women) and > 450 msec (for men) corrected for heart rate using Fridericia’s formula (QTcF, verified on repeat measurements) b. History of QTc prolongation or predisposition for QTc prolongation (clinically relevant ele
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method