A Study of HRXG-K-1939 and Adebrelimab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1, open-label study evaluating the efficacy and safety of HRXG-K-1939 in combination with Adebrelimab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) in patients with advanced solid tumors. HRXG-K-1939 will be administered to patients in a dose escalation regimen to determine a recommended dose for expansion.

Official Title
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A Phase 1 Study to Evaluate the Efficacy and Safety of HRXG-K-1939 and Adebrelimab in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: HRXG-K-1939
* Drug: Adebrelimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily signed the informed consent form and complied with protocols requirements; Patients with advanced solid tumors that are suitable for immunotherapy; ECOG Performance Status of 0 or 1; Life expectancy ≥ 12 weeks; At least one measurable disease per RECIST v1.1; Tumor specimen availability; Adequate marrow and organ function; Have resolution of toxic effects from prior therapy to Grade 1 or less (except for Grade ≤2 alopecia or neuropathy) per CTCAE v5.0; Patients with fertility are willing to use an adequate method of contraception. Exclusion Criteria: Previously detected positive driver genes (EGFR, ALK, ROS1, etc.); Have leptomeningeal, or actively progressing CNS metastases (patients with stable brain metastases can be enrolled); Uncontrolled pleural effusion, pericardial effusion, or ascites; Major surgical procedure within 28 days prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study; Prior anti-cancer therapy (e.g., chemotherapy, radiotherapy, hormonal therapy, targeted therapy, immunotherapy, any other investigational or immunomodulatory drugs) within 21 days prior to initiation of study treatment; Live-attenuated vaccination within 28 days prior to initiation of study treatment through 60 days after the end of study; Systemic steroid therapy or other form of immunosuppressive therapy within 14 days prior to initiation of study treatment; Any history of an immune-mediated Grade 4 adverse event or Grade 3 adverse event that resulted in permanent discontinuation; Active or history of autoimmune disease; Active tuberculosis or infection requiring treatment; History of interstitial lung disease; Allergic to research drug ingredients; Prior malignancy within 5 years prior to study entry; Solid organ or allogeneic bone marrow transplant; HIV positive, HCV positive, HBV DNA copies ≥ 10^3; Significant cardiovascular disease; Other situations that are not suitable for inclusion in this study judged by 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRXG-K-1939 Combined with Adebrelimab<br>Dose Escalation: HRXG-K-1939 at escalated dosages with Adebrelimab Experimental: Dose Expansion HRXG-K-1939 at recommended dose with Adebrelimab | Drug: HRXG-K-1939<br>* HRXG-K-1939<br>* Other names: HRXG-K-1939 is a mRNA cancer vaccines;Drug: Adebrelimab<br>* Adebrelimab is a programmed death-ligand 1 antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation Phase:RP2D | Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of HRXG-K-1939 | 9 months | 
| • Dose Expansion Phase: Antigen-Specific T-cell Responses in Peripheral Blood | • Dose Expansion Phase: Antigen-Specific T-cell Responses in Peripheral Blood | Baseline through 12 months after last HRXG-K-1939 dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | The proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1. | 12 months | 
| Disease Control Rate (DCR) | The proportion of patients who have a CR or PR or SD, as determined by the Investigator at local site per RECIST 1.1. | 12 months | 
| Duration of Response (DoR) | Time from the date of first documented response until the date of documented progression or death in the absence of disease progression. | 12 months | 
| Progression Free Survival (PFS) | Time to progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause. | 12 months | 
| Overall Survival (OS) | Time to death due to any cause | 24 months | 
| Adverse Events(AEs) | Occurrence of Adverse Events(AEs) graded according to CTCAE v5.0 | From consent to 90 days after the final dose of study drug | 
| Biomarker analysis | Serum cytokines (IL-10, IL-6, IL-2, TNF- α, IFN- γ ) Changes from baseline condition | Baseline through 12 months after last HRXG-K-1939 dose |