A Study to Efficacy and Safety of SPH4336 Monotherapy or in Combination With Cadonilimab in Patients With Advanced Solid Tumors.

Study Overview
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Brief Summary
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This is a randomized, Open-label, Phase Ib/IIa study to evaluate the efficacy and safety of SPH4336 monotherapy or in combination with Cadonilimab in the patients with selected advanced solid tumors.

Official Title
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A Randomized, Open-label, Phase Ib/IIa Clinical Study to Evaluate the Efficacy and Safety of SPH4336 Monotherapy or in Combination With Cadonilimab in Patients With Advanced Solid Tumors, Including Advanced Well Differentiated/Dedifferentiated Liposarcoma.

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SPH4336
* Drug: Cadonilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily participate in this study and sign informed consent. Expected survival ≥3 months. Patients with advanced solid tumors (including advanced Well differentiated/dedifferentiated liposarcoma) who cannot be treated by radical surgery/other local treatment. According to RECIST v1.1, participants in the dose expansion phase must have at least one measurable lesion. The laboratory test results meet the organ function requirements before starting the study treatment. Prior to the start of the study treatment, the peripheral nerve toxicity of previous anti-tumor drug treatment had returned to ≤ grade 2, and other reversible toxic reactions had returned to ≤ grade 1, but hair loss/pigmentation and other effects were assessed by the investigator as beneficial to the subjects receiving the study treatment. The toxicity of the risk is not subject to this limitation. Subjects agree to use effective contraception from the time they sign the informed consent to the last time they use the study drug. Exclusion Criteria: Taking anti-tumor traditional Chinese medicines at the time of signing the ICF. Had undergone surgery prior to treatment and hasn't yet recovered from adverse effects of surgery. Had a history of other malignancies before starting the study. History of myocardial infarction, unstable angina pectoris, severe arrhythmia, and symptomatic congestive heart failure before the start of study treatment; NYHA Class ≥II; QTcF≥ 470 ms; LVEF≤ 50%. Diseases affecting drug administration or gastrointestinal absorption before the start of the study and assessed by the investigators could not be included in the study. Previous history of organ transplantation. Before starting the study, HBsAg positive patients with HBV DNA > 500IU/ mL or 2500 copies /mL or the lower limit of the study center detection, or HCV antibody positive patients with HCV RNA positive, or known HIV-infected patients, or known active tuberculosis. Accompanied by any other serious, progressive, or uncontrolled disease. Subjects with a known history of immune-related adverse events that the investigator determined could not be included. History of severe allergic disease, history of severe drug allergy, or known allergy to any component of the investigational product. Women who are pregnant or breastfeeding. Any other reason for which patients are ineligible for the study as assessed by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPH4336<br> | Drug: SPH4336<br>* SPH4336 Tablets ：Orally, 400mg once a day ; 28 days/cycle<br>|
| Experimental: Cadonilimab<br> | Drug: Cadonilimab<br>* Intravenous infusion, 6mg/Kg,28 days/cycle<br>|
| Experimental: SPH4336+ Cadonilimab<br> | Drug: SPH4336<br>* SPH4336 Tablets ：Orally, 400mg once a day ; 28 days/cycle<br>Drug: Cadonilimab<br>* Intravenous infusion, 6mg/Kg,28 days/cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | From the start date of study treatment to the date of progression disease or death , whichever occurred first. | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1. | Approximately 2 years | 
| progression-free rate（PFR） | Proportion of subjects who were alive and free of disease progression from the first use of the investigational drug to 12 weeks. | Approximately 2 years | 
| Cmax | PK (Pharmacokinetics) parameters. | Approximately 2 years | 
| Tmax | PK (Pharmacokinetics) parameters. | Approximately 2 years | 
| Disease control rate (DCR) | DCR was defined as the percentage of patients who have achieved complete response, partial response and stable disease. | Approximately 2 years | 
| Duration of remission (DOR) | DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response to the date of disease progression per RECIST v1.1 or death from any cause. | Approximately 2 years | 
| Overall Survival (OS) | Determination of the overall survival times of all patients. | Approximately 8 years | 
| Incidence of Adverse event | Safety and tolerability | Approximately 2 years |