Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Solid Tumor Cancer
Conditions
Brief summary
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).
Detailed description
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.
Interventions
DRUGRP903
Ia:RP903 50mg, 100mg, 200mg, 300mg,350mg,or other dose, po qd for each 28-day cycle； Ib: RP903,RP2D,po qd for each 28-day cycle
Sponsors
Risen (Suzhou) Pharma Tech Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
once daily on Days 1-28 of each 28-day cycle
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ib:objective response rate(ORR); | 2 years | Efficacy evaluated by the investigator according to RECIST v1.1: objective response rate (ORR); |
| Ia:RP2D | 2 years | Recommended Phase II Dose(RP2D) |
| Ia: MAD | 2 years | Maximum Administrated Dose(MAD) |
| Ib:SAE | 2 years | Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE |
| Ib:AE | 2 years | Type, frequency, duration, severity and characteristics of Adverse Events (AEs) according to NCI-CTCAE |
| Ia:dose-limiting toxicity(DLTs) | 28 days | Incidence and severity of dose-limiting toxicity (DLTs) |
| Ia:Adverse Events | 2 years | Incidence and severity of Adverse Events(AEs) according to NCI-CTCAE |
| Ia: serious adverse events | 2 years | Incidence and severity of serious adverse events(SAEs) according to NCI-CTCAE |
| Ia: Abnormal changes in Laboratory test and other abnormalities | 2 years | Incidence and severity of abnormal changes in Laboratory test and other tests with clinically significant according to NCI-CTCAE |
| Ia: MTD | 2 years | Maximum Tolerated Dose(MTD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ia:Vd/F | 1 years | distribution volume |
| Ia:CL/F | 1 years | clearance |
| Ia:t1/2 | 1 years | half-life |
| Ia:Rac | 1 years | cumulative factor |
| Ia:ORR | 1 years | objective response rate |
| Ia:DoR | 1 years | duration of response |
| Ia:DCR | 1 years | disease control rate |
| Ia:TTR | 1 years | time to response |
| Ia:PFS | 1 years | progression-free survival |
| Ia:OS | 1 years | overall survival |
| Ib:safety:AE | 2 years | Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE |
| Ib:safety:SAE | 2 years | Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE |
| Ib:safety:Body temperature | 2 years | Body temperature changes according to NCI-CTCAE |
| Ib:DoR | 1 years | duration of response |
| Ib:safety:pulse | 2 years | pulse changes according to NCI-CTCAE |
| Ib:safety:respiratory rate | 2 years | respiratory rate changes according to NCI-CTCAE |
| Ib:safety: blood pressure | 2 years | blood pressure changes according to NCI-CTCAE |
| Ib:safety:laboratory test | 2 years | laboratory test changes according to NCI-CTCAE |
| Ib:safety:heart rate | 2 years | heart rate changes according to NCI-CTCAE |
| Ib:safety:QT | 2 years | QT changes according to NCI-CTCAE |
| Ib:safety:QTcF | 2 years | QTcF changes according to NCI-CTCAE |
| Ib:Concentrations of RP903 or its metabolites | 1 years | Concentrations of RP903 or its metabolites (if applicable) in individual subjects at different time points after dosing. |
| Ib:safety:PR | 2 years | PR changes according to NCI-CTCAE |
| Ib:DCR | 1 years | disease control rate |
| Ib:TTR | 1 years | time to response |
| Ib:PFS | 1 years | progression-free survival |
| Ib:OS | 2 years | overall survival |
| Ia:the concentration of RP903 or its metabolites (if applicable) | 1 years | the concentration of RP903 or its metabolites (if applicable) in individual subjects at different time points after administration; |
| Ia:Cmax | 1 years | peak concentration |
| Ia:Ctrough | 1 years | trough concentration |
| Ia:Tmax | 1 years | time to peak |
| Ia:AUC0-t and AUC0-∞ | 1 years | area under the plasma drug concentration-time curve |
Other
| Measure | Time frame | Description |
|---|---|---|
| blood glucose | 28days | To explore the relationship between blood glucose levels in peripheral blood and efficacy; |
| peripheral blood PIK3CA mutation | 28days | To explore the correlation between peripheral blood PIK3CA mutation and efficacy; |
| PIK3CA mutation status | 28days | To explore the correlation between peripheral blood and tumor tissue PIK3CA mutation status in different indications; |
| C-peptide | 28days | To explore the relationship between C-peptide levels in peripheral blood and efficacy; |
| Insulin | 28days | To explore the relationship between Insulin levels in peripheral blood and efficacy; |
Countries
China
Outcome results
None listed