A Study of SHR-1802 in Combination With Adebrelimab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The aim of this study is to observe and evaluate the tolerability, safety, pharmacokinetics and immunogenicity of SHR-1802 combined with adebrelimab in patients with advanced solid tumors, determine the RP2D of SHR-1802 combined with adebrelimab ± chemotherapy, and evaluate the efficacy of SHR-1802 combined with adebrelimab ± chemotherapy in patients with advanced solid tumors.

Official Title
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An Open Label, Multicenter, Phase Ib/II Study of SHR-1802 in Combination With Adebrelimab in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Biological: Adebrelimab
* Biological: SHR-1802
* Drug: Carboplatin/Cisplatin
* Drug: Paclitaxel/Nab-Paclitaxel/Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent； Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Has a life expectancy≥ 12 weeks； At least one measurable lesion according to RECIST v1.1； Pathologically confirmed advanced solid tumor； Adequate bone marrow reserve and organ function. Exclusion Criteria: Have received anti-PD-1 or PD-L1 antibody therapy; Subjects with other malignant tumors in the past 3 years; Have uncontrolled clinically symptomatic pleural effusion, pericardial effusion, or ascites; Previous or current interstitial pneumonia/interstitial lung disease ; History of autoimmune disease with the possibility of recurrence or active autoimmune disease; Severe infection within 1 month before the first study drug administration; The presence of other serious physical or mental disorders or abnormalities in laboratory tests that may increase the risk of study participation or interfere with study results, as well as patients deemed unsuitable for study participation 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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Dose-exploration：Six patients will be enrolled for tolerability observation. If ≥2 subjects in the previous dose level experienced DLTS, an additional 6 subjects in the other dose level were enrolled. Efficacy-expansion: After determination of the recommended dose for Phase II (RP2D), selected cohorts with different tumor types will be expanded.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phase Ib：SHR-1802+Adebrelimab<br> | Biological: Adebrelimab<br>* Specified dose on specified days<br>Biological: SHR-1802<br>* Specified dose on specified days<br>|
| Experimental: phase II cohort 1: SHR-1802+Adebrelimab<br> | Biological: Adebrelimab<br>* Specified dose on specified days<br>Biological: SHR-1802<br>* Specified dose on specified days<br>|
| Experimental: phase II cohort 2: SHR-1802+Adebrelimab + Platinum Doublet Chemotherapy (PDCT)<br> | Biological: Adebrelimab<br>* Specified dose on specified days<br>Biological: SHR-1802<br>* Specified dose on specified days<br>Drug: Carboplatin/Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel/Nab-Paclitaxel/Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|
| Experimental: phase II cohort 3: SHR-1802+Adebrelimab + PDCT<br> | Biological: Adebrelimab<br>* Specified dose on specified days<br>Biological: SHR-1802<br>* Specified dose on specified days<br>Drug: Carboplatin/Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel/Nab-Paclitaxel/Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|
| Experimental: phase II cohort 4: SHR-1802+Adebrelimab<br> | Biological: Adebrelimab<br>* Specified dose on specified days<br>Biological: SHR-1802<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) |  | 3 weeks | 
| Recommended phase II dose (RP2D) |  | up to 2 months | 
| ORR | Objective Response Rate, determined according to RECIST v1.1 criteria | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOR | Duration of Response, determined according to RECIST v1.1 criteria | up to 2 years | 
| DCR | Disease Control Rate, determined according to RECIST v1.1 criteria | up to 2 years | 
| PFS assessed by investigator | Progression Free Survival, determined according to RECIST v1.1 criteria | up to 2 years | 
| TTR | Time to Response，determined according to RECIST v1.1 criteria | up to 2 years | 
| OS (overall survival) | From date of treatment start to any cause death or last follow-up | up to 2 years | 
| 12-month OS rate |  | from the date of the first dose up to 2 years |