SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST

Inclusion Criteria

• •Age minimum of 18 years
• •Histologically confirmed, inoperable or metastatic GIST with an exon 11 or exon 9 primary KIT mutation. Other primary KIT mutations (e.g., exon 13, exon 17) will be considered on a case-by-case basis after discussion with the Principal Investigator. Pathology reports including mutational analysis should be available for review by the Sponsor.
• •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (See Appendix A).
• •Prior progression on or intolerance to imatinib. Imatinib intolerance is defined as discontinuation of imatinib due to an adverse event(s) related to treatment with imatinib that was not manageable with dose modifications.
• •Documented disease progression on sunitinib of at least 25 mg daily as continuous treatment, or 37.5 mg daily with the 4 weeks on/2 weeks of schedule.
• •At least one site of measurable disease on CT/MRI scan as defined by modified RECIST version 1.1 (mRECIST v1.1) criteria.
• •Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including clinically significant laboratory abnormalities, prior to the first dose of the study drug.
• •Adequate organ function:
• •Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (unsupported for 7 days, or 14 days if pegfilgrastim was administered)
• •Platelets ≥ 100 x 109/L (unsupported for 14 days)
• •Hemoglobin ≥8 g/dL (unsupported for 14 days)
• •ALT and AST ≤ 2.5 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN in the presence of hepatic metastases.
• •Serum bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study provided that direct bilirubin ≤1.5 x institutional ULN and indirect bilirubin ≤3 x institutional ULN
• •Estimated glomerular filtration rate ≥45 mL/min/1.73 m2
• •Ability and willingness to provide written, voluntary informed consent
• •Ability to swallow pills
• •For male subjects, unless having undergone permanent sterilization (includes bilateral orchidectomy), agreement to use effective barrier contraception (i.e., condoms) during the study treatment period and for 6 weeks after the last dose of study drug.
• •For women of childbearing potential (WOCBP), confirmation of negative serum or urine pregnancy test prior to dosing with the study drug and agreement to the use of highly effective method of contraception with or without a barrier contraception method during the study treatment period and for 6 weeks after the last dose of the study drug. Female subjects who are using hormonal contraception must agree to remain on a stable regimen throughout the study unless a change is deemed medically necessary by the Investigator.
• •WOCBP are defined as defined as physiologically and anatomically capable of becoming pregnant, unless they meet one of the following conditions:
• •Postmenopausal: 12 months of natural (spontaneous) amenorrhea without an alternative medical cause
• •Prior hysterectomy
• •Prior bilateral oophorectomy
• •Prior bilateral salpingectomy
• •Highly effective methods of birth control includes:
• •Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, delivered orally, intravaginally, or transdermally
• •Progestogen-only hormonal contraception associated with inhibition of ovulation, delivered orally, via injection, or implanted
• •An intrauterine device (IUD)
• •An intrauterine hormone-releasing system (IUS)
• •Bilateral tubal occlusion
• •Vasectomized partner - provided the partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success
• •Sexual abstinence, when consistent with the preferred and usual lifestyle of the subject, can be considered acceptable based on the evaluation of the Investigator, who should take into consideration the duration of the clinical study. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation) and withdrawal are not considered acceptable methods of contraception.
• •* Life expectancy of \> 12 weeks
• •* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• •* Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical or radiographic progression at the time of enrollment.