Open Label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of CYH33, an Oral PI3K Inhibitor in Combination With Olaparib, an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.
The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA mutations, in patients who have progressed on prior PARP inhibitor, and in patients with recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are platinum resistant or refractory. The study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.
∙ Patients eligible for inclusion in this study have to meet all of the following criteria:
• Provide informed consent voluntarily.
• Male and female patients ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is \> 18 years).
• Patients with advanced solid tumor who have failed at least one line of prior systemic therapy or for whom standard therapy do not exist and meet the following eligibility for the corresponding part of the study:
‣ Patient must have a histologically or cytologically confirmed diagnosis of advanced recurrent or metastatic solid tumor.
⁃ At least one measurable lesion as per RECIST 1.1. (Ovarian cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via CA125 GCIG criteria; Prostate cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via PSA response).
⁃ Population eligibility:
• Patients eligible for Part 1 dose escalation: Advanced solid tumors with any DDR gene 1) or PIK3CA 2) mutation who have failed or cannot tolerate standard treatment or currently have no standard treatment.
∙ Patients eligible for Part 2 dose expansion:
‣ Cohort 1: Advanced solid tumors with any selected DDR3) gene mutation
⁃ Cohort 2: Advanced solid tumors with PIK3CA hotspot mutation
⁃ Cohort 3: Advanced high grade serous ovarian, fallopian tube or primary peritoneal cancer patients with acquired PARP inhibitor resistance4)
⁃ Cohort 4: Advanced solid tumors with any selected DDR3) gene mutation with acquired PARP inhibitor resistance4).
⁃ Cohort 5: Platinum resistant/refractory5) recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
• Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor tissue sample) or blood samples.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.