A Phase Ib/II Study of SHR-A1811 Injection in Breast Cancer

Study Overview
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Brief Summary
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To evaluate the safety, tolerability and efficacy of SHR-A1811 in combination with pyrotinib or pertuzumab or adebrelimab or albumin-bound paclitaxel in patients with breast cancer.

Official Title
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A Phase Ib/II Multicenter, Open-Label Clinical Trial of SHR-A1811 Injection in Combination With Pyrotinib or Pertuzumab or Adebrelimab or Paclitaxel for Injection (Albumin Bound) in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: SHR-A1811：Pyrotinib
* Drug: SHR-A1811；Pertuzumab
* Drug: SHR-A1811；Adebrelimab
* Drug: SHR-A1811；Albumin paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 to 75 (inclusive) Breast cancer confirmed by histology or cytology. ECOG score is 0 or 1 An expected survival of ≥ 12 weeks At least one measurable lesion according to RECIST v1.1 criteria Have adequate renal and hepatic function Patients voluntarily joined the study and signed informed consent Exclusion Criteria: Have other malignancies within the past 5 years Active central nervous system metastasis without surgery or radiotherapy Presence with uncontrollable third space effusion Have undergone other anti-tumor treatment within 4 weeks before the first dose Immunosuppressant or systemic hormone therapy was used within 2 weeks prior to the first dose Any active autoimmune disease or a history of autoimmune disease A history of immune deficiency Clinically significant cardiovascular disorders Clinically significant history of lung disease The toxicity from previous anti-tumor treatment has not recovered to ≤ grade I Known hereditary or acquired bleeding tendency Active hepatitis and liver cirrhosis Presence of other serious physical or mental diseases or laboratory abnormalities

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

Sexes Eligible for Study
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Female

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
Interventional Model Description: This study is a multicenter, open-label, dose exploration and efficacy expansion phase Ib / II study. The first stage is the dose exploration phase, which uses the 3 + 3 escalation design; The second stage is the curative effect expansion phase.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811combined Pyrotinib<br> | Drug: SHR-A1811：Pyrotinib<br>* SHR-A1811：Lyophilized powder injection, 100mg / bottle, intravenous drip Pyrotinib：Tablet, 160mg / tablet, 80mg / tablet, oral<br>|
| Experimental: SHR-A1811Combined Pertuzumab<br> | Drug: SHR-A1811；Pertuzumab<br>* SHR-A1811：Lyophilized powder injection, 100mg / bottle, intravenous drip Pertuzumab：Injection, 420 Mg (14 ml) / bottle, intravenous drip<br>|
| Experimental: SHR-A1811Combined Adebrelimab<br> | Drug: SHR-A1811；Adebrelimab<br>* SHR-A1811：Lyophilized powder injection, 100mg / bottle, intravenous drip Adebrelimab：Injection, 12ml: 0.6g/bottle, intravenous drip<br>|
| Experimental: SHR-A1811Combined Albumin-bound Paclitaxel<br> | Drug: SHR-A1811；Albumin paclitaxel<br>* SHR-A1811：Lyophilized powder injection, 100mg / bottle, intravenous drip Albumin paclitaxel：Injection, 100mg / box, intravenous drip<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT（Phase I (dose exploration phase) ） |  | 21 days after the first administration of each subject | 
| AE（Phase I (dose exploration phase) ） |  | from Day1 to 40 or 90 days after last dose | 
| Incidence and severity of serious adverse events (SAE)（Phase I (dose exploration phase) ） |  | from Day1 to 40 or 90 days after last dose | 
| Objective response rate（Phase II (efficacy expansion phase)） |  | Two years after the last subject was enrolled in the group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: Cmin of SHR-A1811（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: Cmax of SHR-A1811（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: AUC0-t of SHR-A1811（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: Cmin of Pyrotinib（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: C4h of Pyrotinib（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: Cmin of Adebrelimab（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| Immunogenicity of SHR-A1811（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| Immunogenicity of Adebrelimab（Phase I secondary endpoint） |  | through study completion, an average of 2 years | 
| Objective Response Rate（Phase I secondary endpoint） |  | from first dose to disease progression or death, whichever comes first, up to 3 years | 
| Duration of response（Phase I secondary endpoint） |  | from first dose to disease progression or death, whichever comes first, up to 3 years | 
| Progression Free Survival（Phase I secondary endpoint） |  | from first dose to disease progression or death, whichever comes first, up to 3 years | 
| AE（Phase II secondary study endpoint） |  | from Day1 to 40 or 90 days after last dose | 
| Incidence and severity of serious adverse events (SAE)（Phase II secondary study endpoint） |  | from Day1 to 40 or 90 days after last dose | 
| PK parameter: Cmin, Cmax, and AUC0-t of SHR-A1811（Phase II secondary study endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: Cmin, C4h of Pyrotinib:（Phase II secondary study endpoint） |  | through study completion, an average of 2 years | 
| PK parameter: Cmin of Adebrelimab（Phase II secondary study endpoint） |  | through study completion, an average of 2 years | 
| Immunogenicity of SHR-A1811（Phase II secondary study endpoint） |  | through study completion, an average of 2 years | 
| Immunogenicity of Adebrelimab（Phase II secondary study endpoint） |  | through study completion, an average of 2 years | 
| Duration of response（Phase II secondary study endpoint） |  | from first dose to disease progression or death, whichever comes first, up to 3 years | 
| Progression Free Survival（Phase II secondary study endpoint） |  | from first dose to disease progression, or death, whichever comes first, up to 3 years | 
| Event-Free Survival Rate（Phase II secondary study endpoint） |  | from first dose to disease progression, disease recurrence, or death, whichever comes first, up to 3 years |