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).

Phase Ia is divided into two phases of dose escalation and dose extension: This part includes dose escalation and dose extension of RP903 single agent to investigate the safety, tolerability, maximum tolerated dose and pharmacokinetic (PK) characteristics of RP903 single agent.

Phase Ib is the clinical indication expansion phase, and the primary purpose of this phase is to evaluate the initial safety and anti-tumor efficacy in a selected indication target population. After determining RP903 monotherapy RP2D in Phase Ia, SMC will select four advanced malignant tumors with PIK3CA mutations (cervical cancer, endometrial cancer, breast cancer, and ovarian cancer) as indications for clinical expansion studies based on phase Ia efficacy, safety, and pharmacokinetic (PK) data. The dose was determined according to the results of the dose escalation phase and the dose extension phase.

Inclusion Criteria:

• 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

Exclusion Criteria:

• Patients with known allergy to any component of RP903
• Previously treated with PI3K, mTOR or AKT inhibitors
• Systemic anti-tumor therapy within 4 weeks prior to the first dose
• Presence of leptomeningeal or meningeal metastasis, or presence of signs of carcinomatous Meningitis
• Metastases to bone marrow
• Child-Pugh grade B or C
• Active hepatitis B or C
• History of type I Diabetes mellitus，gestational diabetes or uncontrolled type II Diabetes mellitus