Clinical trial NCT06846099: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Efficacy and Indications of RP903
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ovarian Cancer
Cervical Cancer
Endometrial Cancer
Breast Cancer
Solid Tumor Cancer
Lead sponsor: Risen (Suzhou) Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-02-25
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: once daily on Days 1-28 of each 28-day cycle
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Ia:dose-limiting toxicity(DLTs)
timeFrame: 28 days
measure: Ia:Adverse Events
timeFrame: 2 years
measure: Ia: serious adverse events
timeFrame: 2 years
measure: Ia: Abnormal changes in Laboratory test and other abnormalities
timeFrame: 2 years
measure: Ia: MTD
timeFrame: 2 years
measure: Ia: MAD
timeFrame: 2 years
measure: Ia:RP2D
timeFrame: 2 years
measure: Ib:objective response rate(ORR);
timeFrame: 2 years
measure: Ib:AE
timeFrame: 2 years
measure: Ib:SAE
timeFrame: 2 years
Secondary outcomes:
measure: Ia:the concentration of RP903 or its metabolites (if applicable)
timeFrame: 1 years
measure: Ia:Cmax
timeFrame: 1 years
measure: Ia:Ctrough
timeFrame: 1 years
measure: Ia:Tmax
timeFrame: 1 years
measure: Ia:AUC0-t and AUC0-∞
timeFrame: 1 years
measure: Ia:Vd/F
timeFrame: 1 years
measure: Ia:CL/F
timeFrame: 1 years
measure: Ia:t1/2
timeFrame: 1 years
measure: Ia:Rac
timeFrame: 1 years
measure: Ia:ORR
timeFrame: 1 years
measure: Ia:DoR
timeFrame: 1 years
measure: Ia:DCR
timeFrame: 1 years
measure: Ia:TTR
timeFrame: 1 years
measure: Ia:PFS
timeFrame: 1 years
measure: Ia:OS
timeFrame: 1 years
measure: Ib:safety:AE
timeFrame: 2 years
measure: Ib:safety:SAE
timeFrame: 2 years
measure: Ib:safety:Body temperature
timeFrame: 2 years
measure: Ib:safety:pulse
timeFrame: 2 years
measure: Ib:safety:respiratory rate
timeFrame: 2 years
measure: Ib:safety: blood pressure
timeFrame: 2 years
measure: Ib:safety:laboratory test
timeFrame: 2 years
measure: Ib:safety:heart rate
timeFrame: 2 years
measure: Ib:safety:QT
timeFrame: 2 years
measure: Ib:safety:QTcF
timeFrame: 2 years
measure: Ib:safety:PR
timeFrame: 2 years
measure: Ib:DoR
timeFrame: 1 years
measure: Ib:DCR
timeFrame: 1 years
measure: Ib:TTR
timeFrame: 1 years
measure: Ib:PFS
timeFrame: 1 years
measure: Ib:OS
timeFrame: 2 years
measure: Ib:Concentrations of RP903 or its metabolites
timeFrame: 1 years
Other outcomes:
measure: blood glucose
timeFrame: 28days
measure: Insulin
timeFrame: 28days
measure: C-peptide
timeFrame: 28days
measure: PIK3CA mutation status
timeFrame: 28days
measure: peripheral blood PIK3CA mutation
timeFrame: 28days
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changchun
country: China
facility: Jilin University First Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital & Institute
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical College
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Affiliated Cancer Hospital of Fudan University
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
city: Suining
country: China
facility: Suining Central Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Yinchuan
country: China
facility: Ceneral Hosipital of Ningxia Medical University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
References: