A Phase I/Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Efficacy and Indications of Pl3Kα-Selective Inhibitor RP903 (JS105) in Subjects with Advanced Malignancies
This is an open phase I/Ib clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and initial efficacy of RP903 in patients with advanced malignancies who have failed standard treatment or have no standard treatment options. The study was divided into two parts: dose escalation and dose extension (Phase Ia) and clinical extension (Phase Ib).
• Agreement to provide fresh or archived tumor tissue sample within 3 years
• Ia (dose escalation phase and dose expansion phase):patients with pathologically confirmed advanced Malignant solid tumour who have experienced Treatment failure, are unable to tolerate standard treatment, or have no standard treatment
• Ib: Patients with advanced malignant solid tumours who have PIK3CA activating mutations, experience treatment failure, are intolerant to standard treatment, or have no standard treatment
• Phase Ia: Solid tumour, not limited to specific types; dose expansion phase will prioritize cervix carcinoma, endometrial cancer, ovarian cancer, and breast cancer.
• Phase Ib:Cervix carcinoma (Expanded Cohort 1):Having received first-line (including Platinum-based chemotherapy ± bevacizumab) or second-line treatment and having disease progression during or after treatment; (recurrence during or within 12 months after neoadjuvant or adjuvant treatment in previous treatment will be regarded as one treatment line)
• Phase Ib:Endometrial cancer (extension cohort 2):Progression during or after first-line (including platinum) or second-line treatment of advanced or metastatic disease; (recurrence during or within 12 months after neoadjuvant or adjuvant treatment in previous treatment will be considered as one treatment line);Sarcoma type not included
• Ovarian cancer (expanded cohort 3) (PIK3CA mutation):
• Ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma who have experienced treatment failure or are intolerant to at least one line of cytotoxic therapy ± PARP inhibitor; (recurrence during or within 12 months after neoadjuvant or adjuvant therapy will be considered one line of therapy)
• Pathological types include high-grade serous carcinoma, clear cell carcinoma, or Endometrioid carcinoma
• Breast cancer (extension cohort 4) (PIK3CA mutation):
• Advanced, recurrent and metastatic breast cancer;
• Prior systemic treatment in at least 1 line and no more than 3 lines (patients who have relapsed during or within 12 months after completion of neoadjuvant/adjuvant endocrine therapy will be considered as one line of endocrine therapy)
• At least one measurable lesion as per RECIST v1.1 (except the dose-escalation phase of monotherapy)
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1
• Adequate hematologic and organ function