A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Efficacy and Indications of RP903

Phase 1

Recruiting

• Conditions: Ovarian Cancer; Cervical Cancer; Endometrial Cancer; Breast Cancer; Solid Tumor Cancer
• Interventions: Drug: RP903

• Registration Number: NCT06846099
• Lead Sponsor: Risen (Suzhou) Pharma Tech Co., Ltd.

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.

Study Timeline

• Study Start: 2022-12-07
• Study First Submitted: 2025-01-19
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-20
• Last Update Submitted: 2025-02-20
• Study First Posted: 2025-02-25
• Last Update Posted: 2025-02-25
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 174

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RP903 arm	RP903	Ia:Participants will receive RP903 in escalating dose levels with starting dose of 50mg, po qd for each 28-day cycle Ib:Participants will receive RP903 with RP2D, po qd for each 28-day cycle

Primary Outcome Measures

Name	Time	Method
Ia:dose-limiting toxicity(DLTs)	28 days	Incidence and severity of dose-limiting toxicity (DLTs)
Ia: serious adverse events	2 years	Incidence and severity of serious adverse events(SAEs) according to NCI-CTCAE
Ia: MTD	2 years	Maximum Tolerated Dose(MTD)
Ia:RP2D	2 years	Recommended Phase II Dose(RP2D)
Ib:objective response rate(ORR);	2 years	Efficacy evaluated by the investigator according to RECIST v1.1: objective response rate (ORR);
Ia:Adverse Events	2 years	Incidence and severity of Adverse Events(AEs) 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: MAD	2 years	Maximum Administrated Dose(MAD)
Ib:AE	2 years	Type, frequency, duration, severity and characteristics of Adverse Events (AEs) according to NCI-CTCAE
Ib:SAE	2 years	Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE

Secondary Outcome Measures

Name	Time	Method
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.
Ia:Cmax	1 years	peak concentration
Ia:Tmax	1 years	time to peak
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
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:Ctrough	1 years	trough concentration
Ia:AUC0-t and AUC0-∞	1 years	area under the plasma drug concentration-time curve
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
Ib:safety:Body temperature	2 years	Body temperature changes according to NCI-CTCAE
Ib:safety:pulse	2 years	pulse changes according to NCI-CTCAE
Ib:safety:QTcF	2 years	QTcF changes according to NCI-CTCAE
Ib:safety:PR	2 years	PR 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:DoR	1 years	duration of response
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

Trial Locations

Locations (23)

Beijing Cancer Hospital; 🇨🇳 Beijing, China

The First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu, China

Jilin Cancer Hospital; 🇨🇳 Changchun, China

Jilin University First Hospital; 🇨🇳 Changchun, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, China

Fujian Cancer Hospital; 🇨🇳 Fuzhou, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, China

Sir Run Run Shaw Hospital; 🇨🇳 Hangzhou, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, China

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