A Phase IB/II Clinical Study of SHR-A2009 for Injection in Combination With Other Antitumor Therapies in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is an open-label, multicenter Phase IB/II clinical trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SHR-A2009 for injection in combination with other antitumor therapies in patients with advanced solid tumors.

Official Title
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A Phase IB/II, Open-Label, Multicentre Clinical Study to Evaluate the Safety, Tolerability and Efficacy of SHR-A2009 for Injection in Combination With Other Therapies in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SHR-A2009 for injection ； Almonertinib Mesilate Tablets
* Drug: SHR-A2009 for injection；Adebrelimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 75 years old (inclusive), Female or male Subjects with unresectable locally advanced or metastatic non-small cell lung cancer confirmed by histology or cytology Previously treated by EGFR-TKI or other standard treatment or have not been treated for metastatic setting; At least one measurable tumor lesion according to RECIST v1.1 (enrollment of subjects with only non-target lesions is permitted in Stage IB phase) ECOG performance score of 0-1; Expected survival time ≥ 12 weeks; Adequate bone marrow and organ function Subjects are required to give informed consent for this study prior to the trial and voluntarily sign a written informed consent form. Exclusion Criteria: Subjects with active central nervous system (CNS) metastases. Spinal cord compression not cured by surgery and/or radiotherapy cannot be enrolled. Subjects with uncontrolled tumor-related pain Clinically uncontrollable third space fluid Received antitumor therapy such as chemotherapy within 4 weeks prior to the first dose of study drug; Received >30 Gy of non-thoracic radical radiation therapy within 4 weeks prior to the first administration of study drug; Major organ surgery or significant trauma within 4 weeks prior to first use of study drug; Concomitant other malignancies ≤ 5 years prior to first dose of study drug; Subjects with a history of interstitial pneumonitis or imaging at screening suggestive of suspected interstitial pneumonitis; or other moderate-to-severe lung disease that severely affects lung function Serious cardiovascular disease Presence of refractory nausea, vomiting, chronic gastrointestinal disease, etc.; subjects with active, known or suspected autoimmune diseases Presence of severe infection within 4 weeks prior to first dose of study drug Subjects with clinically significant bleeding symptoms within 3 months prior to the first dose of study drug Arterial/venous thrombotic events within 3 months prior to the first study dose History of immunodeficiency, including a positive HIV test Presence of active hepatitis B or C; History of severe allergic reactions to other monoclonal antibodies or allergic reactions to any component of the SHR-A2009 product. Known history of alcohol or drug dependence or addiction; Persons with mental disorders or poor compliance;

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: Treatment Part A: SHR-A2009 for injection in combination with Almonertinib Mesilate Tablets<br> | Drug: SHR-A2009 for injection ； Almonertinib Mesilate Tablets<br>* Phase IB: SHR-A2009 will be administered intravenously，Almonertinib Mesilate Tablets will be administered orally. 2 or 3 dose levels are preset in phase IB. Phase II: 2 dose cohorts will be selected and it's randomization.<br>|
| Experimental: Treatment Part B: SHR-A2009 for injection in combination with Adebrelimab Injection<br> | Drug: SHR-A2009 for injection；Adebrelimab Injection<br>* Phase IB: SHR-A2009 and Adebrelimab will be administered intravenously. 2 dose levels are preset in phase IB. Phase II: RPD2 will be selected to evaluate preliminary efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) (phase IB) |  | 21 days after the first dose was administered to each subject. | 
| Objective Response Rate (ORR) (phase II). |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: toxin-binding antibody of SHR-A2009 |  | through study completion, an average of 2 years | 
| PK parameter: total antibody of SHR-A2009 |  | through study completion, an average of 2 years | 
| PK parameter: free toxin of SHR-A2009 |  | through study completion, an average of 2 years | 
| Plasma concentration of Adebrelimab |  | through study completion, an average of 2 years | 
| Immunogenicity of SHR-A2009 and Adebrelimab (Anti-SHR-A2009 antibody, anti- Adebrelimab antibody ) (Phase IB) |  | through study completion, an average of 2 years | 
| Duration of response(DoR ) |  | One year after the last subject was enrolled in the group | 
| Progression Free Survival(PFS) |  | 2 years after the last subject was enrolled in the group | 
| Objective response rate |  | 2 years after the last subject was enrolled in the group | 
| overall survival (OS) (phase IB) |  | 3 years after the last subject was enrolled in the group | 
| Incidence of AEs（Phase II (efficacy expansion phase)） |  | from Day1 to 90 days after last dose | 
| Incidence of SAEs（Phase II (efficacy expansion phase)） |  | from Day1 to 90 days after last dose |