SC0191 Plus Chemotherapy in Advanced Ovarian Canceradvanced Ovarian Cancer

Study Overview
=================
Brief Summary
-----------------
A phase Ib/II clinical study on the safety, pharmacokinetic characteristics, and preliminary efficacy of SC0191 combination chemotherapy in patients with advanced ovarian cancer.

Detailed Description
-----------------
The phase 1b/2,multicenter, open-label study, contains 2 parts. Part 1 Dose Escalation of SC0191 combination chemotherapy: Part 1 will estimate the RP2D in dose escalation cohorts in patients withadvanced ovarian cancer. Part 2 Dose Expansion of SC0191 plus Chemotherapy.

Official Title
-----------------
A Phase Ib/II Clinical Study on the Safety, Pharmacokinetic Characteristics, and Preliminary Efficacy of SC0191 Combination Chemotherapy in Patients With Advanced Ovarian Cancer.

Conditions
-----------------
Serous Ovarian Cancer, Advanced Ovarian Cancer

Intervention / Treatment
-----------------
* Drug: SC0191
* Drug: Gemcitabine
* Drug: Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed advanced ovarian cancer that has failed or intolerant or not applicable to standard treatment (applicable to the dose escalation phase of stage Ib); Histologically or cytologically confirmed advanced high-grade serous ovarian cancer, platinum-resistant or platinum-refractory recurrent ovarian cancer (applicable to the dose expansion phase of stage II); There is at least one measurable lesion that meets the definition of RECIST 1.1; Voluntarily participate in clinical trials and sign informed consent; Age ≥18 years; ECOG score of 0 to 1; Predicted life expectancy ≥3 months; Adequate bone marrow, liver biochemistry, renal function, and coagulation status. Female patients who agree to use adequate contraceptive measures. Exclusion Criteria: Received chemotherapy, radiotherapy, immunotherapy or biological therapy, steroid therapy or other investigational drugs <28 days prior to the first dose of study treatment. Patients who have not fully recovered from surgery according to the investigator's judgment.; Patients who have previously received WEE1 inhibitor treatment; Unresolved AEs or toxicities due to previous treatments; Patients with contraindications or a history of severe allergies to gemcitabine or paclitaxel; Known malignant CNS disease other than neurologically stable, treated brain metastases; Other medical conditions or systemic diseases not suitable to participate; The need for long-term therapeutic doses of anticoagulant or antiplatelet drugs; Received CYP3A4 moderate or strong inhibitors or CYP3A4 moderate or strong inducers within 14 days; Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (SC0191 + Gemcitabine).<br>SC0191 PO will be taken on days 1-3, 8-10, and 15-17 of each 28 day cycle. Gemcitabine 1000 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle. | Drug: SC0191<br>* SC0191 PO will be taken on days 1-3, 8-10, and 15-17 of each 28 day cycle.<br>* Other names: Study drug;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.<br>* Other names: Gemcitabine Injection;|
| Experimental: Arm B (SC0191 + Paclitaxel).<br>SC0191 PO will be taken on days 1-3, 8-10, and 15-17 of each 28 day cycle. Paclitaxel 80 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle. | Drug: SC0191<br>* SC0191 PO will be taken on days 1-3, 8-10, and 15-17 of each 28 day cycle.<br>* Other names: Study drug;Drug: Paclitaxel<br>* Paclitaxel 80 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.<br>* Other names: Taxol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of SC0191 in combination with gemcitabine or paclitaxel | ncidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 | From the first dose of study treatment until 30 days after the last dose. | 
| To identify the recommended Phase 2 dose (RP2D) of SC0191 in combination with gemcitabine or paclitaxel | Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1 | Through Cycle 1 (cycle is 28 days） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the plasma pharmacokinetics (PK) of SC0191 in combination with gemcitabine or paclitaxel | Plasma pharmacokinetics (PK) of SC0191 in combination with chemotherapy: Single Dose SC0191 Cmax, Tmax, t1/2,AUC0-24h, AUC0-last, CL/F, Vd/F, and steady state SC0191 Ctrough, Cmax,ss, Cavg,ss, Tmax,ss, AUC0-τ, Rac. | Through Cycle 1 (cycle is 28 days） | 
| To obtain estimates of clinical activity by determining the objective response rate (ORR) of SC0191 in combination with gemcitabine or paclitaxel | Objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1 | Through completion | 
| To obtain estimates of clinical activity by determining the time to CA125 progression of SC0191 in combination with gemcitabine or paclitaxel | Time to CA125 progression according to the Gynecologic Cancer Intergroup (GCIG) criteria | Through completion | 
| To obtain estimates of clinical activity by determining the progression-free survival (PFS) of SC0191 in combination with gemcitabine or paclitaxel | Progression-free survival (PFS) as defined by RECIST version 1.1 and clinical criteria | Through completion | 
| To obtain estimates of clinical activity by determining the duration of response (DOR) of SC0191 in combination with gemcitabine or paclitaxel | Duration of response (DOR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1 | Through completion | 
| To obtain estimates of clinical activity by determining the disease control rate (DCR) of SC0191 in combination with gemcitabine or paclitaxel | Disease control rate (DCR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1 | Through completion |