KD6001 in Combination With Anti-PD-1 Antibody±Bevacizumab in Patients With Advanced HCC and Other Solid Tumors

Study Overview
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Brief Summary
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This is a phase 1b/2, open label study to evaluate the safety, tolerability, pharmacokinetics and initial efficacy of KD6001 in combination with Tislelizumab ± Bevacizumab in patients with Advanced HCC and Other Solid Tumors.

Official Title
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Efficacy of KD6001 in Combination With Tislelizumab±Bevacizumab in Patients With Advanced HCC and Other Solid Tumors

Conditions
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Advanced HCC, Other Solid Tumors

Intervention / Treatment
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* Drug: KD6001
* Drug: Tislelizumab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Being voluntary to sign the informed consent form. Male or female, aged ≥ 18 years. Patients whose estimated survival time is more than 3 months. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1. At least one measurable lesion is used as the target lesion according to the Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST V1.1). Histologically or cytologically confirmed advanced solid tumors. Have a current liver function meeting Child Pugh Class A in patients with HCC. Part A: Advanced solid tumors. PartB/C: HCC. Patients will agree to provide tumor tissue samples. The results of laboratory examination during the screening period suggest that the subjects have good organ function. Male subjects with reproductive ability or female subjects with the possibility of pregnancy use effective contraceptive methods. Good compliance and follow-up. Main Exclusion Criteria: History of malignancy other than the disease under study within 5 years prior to screening，except those malignancies that are expected to be cured after treatment. Systematic treatment with antitumor drugs within 4 weeks prior to the start of this study. Prior treatment with anti-CTLA-4 antibody. Adverse events caused by prior treatment did not recovered to NCI-CTCAE v5.0 grade 1 and below. Subjects with CNS metastases or leptomeningeal disease. Subjects with an active, known or suspected autoimmune disease. Subjects with acute or chronic active hepatitis B or hepatitis C. Has histological or cytological diagnosis of fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma. Subjects suffers from severe cardiovascular and cerebrovascular diseases. History or evidence of bleeding diathesis or significant coagulopathy at risk of bleeding. Subjects with an active infection requiring systemic treatment. Known history of testing positive for human immunodeficiency virus (HIV). Subjects known to have active tuberculosis (TB). Pregnant or breastfeeding females. Known to be allergic to KD6001, tislelizumab, bevacizumab or its components.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1：KD6001+Tislelizumab<br>KD6001 combined with Tislelizumab in patients with solid tumors（hepatocellular carcinoma, esophageal squamous cell carcinoma, MSI-H or dMMR solid tumors are preferentially included） | Drug: KD6001<br>* KD6001 will be administered intravenously.<br>Drug: Tislelizumab<br>* Tislelizumab will be administered intravenously.<br>|
| Experimental: Phase 2：KD6001+Tislelizumab±Bevacizumab<br>KD6001 combined with Tislelizumab±Bevacizumab in patients with advanced HCC | Drug: KD6001<br>* KD6001 will be administered intravenously.<br>Drug: Tislelizumab<br>* Tislelizumab will be administered intravenously.<br>Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) | DLTs will be assessed during the dose-escalation phase and are defined as the following treatment-related adverse events occurring within a total of 21 days after the first trial administration. | Up to Day 21 | 
| The incidence and safety profile of participants with adverse events (AEs), serious adverse events(SAE), and immune-related adverse event(irAE) | Evaluate the adverse events (AE) according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (NCI CTCAE 5.0). | Baseline to study completion up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The antitumor activity of KD6001 in combination with Tislelizumab ± Bevacizumab measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Number of participants with response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. | Baseline to study completion up to 2 years | 
| Maximum Plasma Concentration [Cmax] | The PK profile of KD6001 in combination with Tislelizumab ± Bevacizumab. | Baseline to study completion up to 2 years | 
| Time to reach maximum serum concentration (Tmax) | The PK profile of KD6001 in combination with Tislelizumab ± Bevacizumab. | Baseline to study completion up to 2 years | 
| Half-life (T1/2) | The PK profile of KD6001 in combination with Tislelizumab ± Bevacizumab. | Baseline to study completion up to 2 years | 
| Area under blood concentration-time curve(AUC0-T and AUC0-∞) | The PK profile of KD6001 in combination with Tislelizumab ± Bevacizumab. | Baseline to study completion up to 2 years | 
| Apparent volume of distribution (Vd) | The PK profile of KD6001 in combination with Tislelizumab ± Bevacizumab. | Baseline to study completion up to 2 years | 
| The immunogenicity of KD6001 in combination with Tislelizumab ± Bevacizumab | Including the incidence of ADA positive. For ADA positive patients, the incidence of neutralizing antibody (Nab) will be analyzed. | Baseline to study completion up to 2 years |