advanced solid tumor
Conditions
Interventions
dose esclation( Phase I): Multiple doses (25~600 mg) of BYS10
dose expansion (Phase II):BYS10 (recommended Phase 2 dose)
Sponsors
Cancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subjects has provided informed consent prior to initiation of any procedures in this study. 2. Male or female aged 18-75 years old. 3. Patients with locally advanced/metastatic solid tumors confirmed by histology and/or cytology. Phase I: Patients with a locally advanced or metastatic solid tumor who have progressed or no response of standard or available curative therapy, are unsuitable or are unable to tolerate standard of care therapy, or unable to obtain standard therapy. Phase II: All subjects must have locally advanced/metastatic solid tumors with RET fusions or mutations (excluding synonymous, shifted code and nonsense mutations) by tumor histologic genetic testing (central laboratory), including the following cohorts: Cohort 1: RET gene fusion non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. Cohort 2: Medullary thyroid carcinoma (MTC) with RET gene mutation treated with multi-targeted tyrosine kinase inhibitors (vandetanib and/or cabozantinib, anlotinib, sorafenib, sulfatinib, lenvatinib). Cohort 3: RET gene fusion thyroid cancer (TC) treated with first-line standard therapy (those suitable for radioiodine treatment must be radioiodine-refractory). Cohort 4: Other advanced solid tumors with RET gene abnormalities that have been treated with first-line standard therapy (unless no standard therapy is available or the investigator deems standard therapy inappropriate); 4. Patients who have previously received a multiple kinase inhibitor (MKI) with RET inhibitory activity may be enrolled, and the specific drug definition may be determined by the principal investigator in consultation with the sponsor; 5. At least one measurable lesion during the screening period according to RECIST 1.1 standard or Response Assessment in Neurological Tumors (RANO) standard (for intracranial primary tumors); 6. ECOG score 0~1; 7. Life expectancy =3 months;; 8. Basic normal function of the major organs and laboratory test values during the screening period; 9. Patient agrees to provide archived tumor tissue samples or conduct tumor tissue biopsy (Phase I only: if fresh and archived tissues are not available, patients can be enrolled after consultation and agreement with the sponsor); 10. Blood human chorionic gonadotropin (hCG) pregnancy test results must be negative for female subjects of childbearing age during the screening period; 11. Subjects agree to use adequate contraceptive methods from the time they sign the informed consent until 6 months after the last dose. This includes, but is not limited to: abstinence, vasectomy in men, female sterilization, effective IUDs, and effective contraceptive medications;
Exclusion criteria
Exclusion criteria: 1. Patient received the following anticancer therapy: Any systemic anticancer therapy (except for immunotherapy or other antibody therapies) and all forms of radiotherapy, within 14 days or 5 half-lives prior to the first dose of study drug. Any immunotherapy or other antibody therapy within 28 days prior to the first dose of study drug (immune related toxicities must have resolved to 470 msec during the screening period >470msec, or being treated with a drug known to prolong the QT/QTc interval, or the presence of other factors that may prolong the QTc interval; 8. Patient has central nervous system (CNS) metastases or a primary CNS tumor with the following exceptions: those who are asymptomatic on stable doses of steroids [=4 mg/day of dexamethasone or equivalent doses of other hormones) maintained or reduced for more than 2 weeks, or those who do not require steroid therapy; 9. Patients have difficulty swallowing, or have a gastrointestinal condition that alter the drug absorption and is in an acute exacerbation (such as Crohn's disease, ulcerative colitis, or short bowel syndrome), or have other malabsorption condition; 10. Patients with a history of interstitial lung disease requiring treatment, history of radiation pneumonia, or clinically active interstitial lung disease (interstitial lung disease, interstitial lung fibrosis known from Phase I studies, or prior history of pneumonia due to tyrosine kinase inhibitors); 11. History of severe allergy, or hypersensitivity to any active or inactive component of the study drug; 12. Patients with any prior treatment-induced adverse events and/or complications have not recovered to normal or = Grade 1 prior to the first dose. Patients with hair loss, pigmentation (of any grade), or peripheral sensory neuropathy (= grade 2) can be enrolled; 13. Patients who participated in other clinical trials within 4 weeks prior to the first dose (except for screening failures). 14. HIV infection, syphilis infection, HCV inf
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and category of dose limiting toxicity (DLTs);Adverse event;Serious adverse event;Objective response rate , ORR;Progression-free survival ,PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters;disease control rate, DCR;Overall Survival, OS;RET gene status;PD marker;Clinical Benefit Rate, CBR;Time to Response,TTR;Duration of Response, DOR;Objective response rate , ORR; | — |
Countries
China
Contacts
Public ContactJie He
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed