A Trial of Injectable SHR-A1811 in Combination With Pyrotinib or SHR-1316 in Subjects With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This study was an open, multicenter, dose-increasing/investigational Phase IB/II clinical trial to evaluate the efficacy of SHR-A1811 in combination with other antitumor therapies in subjects with advanced non-small cell lung cancer with HER2 . It can be divided into two parts, Part A is the dose escalation and efficacy exploration study of SHR-A1811 combined with Pyrotinib, and Part B is the dose escalation and efficacy exploration study of SHR-A1811 combined with SHR-1316.

Official Title
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Phase IB/II Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of Injectable SHR-A1811 in Combination With Pyrotinib or SHR-1316 in Subjects With Advanced Non-small Cell Lung Cancer With HER2

Conditions
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Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-A1811 & Pyrotinib/SHR-A1811 & SHR-1316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give informed consent, signed and dated IRB/EC approved informed consent, willing and able to comply with treatment planning visits, tests and other procedural requirements When signing the informed consent, the age is 18-75 years old (including both ends), and there is no gender limitation The ECOG score is 0 or 1 The expected survival is ≥12 weeks Subjects with advanced or metastatic non-small cell lung cancer Formalin fixed, paraffin-embedded tumor tissue blocks or sections of unstained tumor specimens are provided Subjects who have failed prior standard care or are intolerant to standard care There is at least one measurable lesion Vital organs are functioning well Heart function is good Agree to birth control Exclusion Criteria: There are untreated or active central nervous system (CNS) tumor metastases Pleural, ascites, or pericardial effusion requiring intervention occurred within 7 days prior to initial administration Systemic antitumor therapy was performed 4 weeks prior to study initiation Prior treatment with antibody-conjugated drugs Received >30 Gy chest radiation within 6 months prior to initial administration Palliative radiotherapy was completed within 7 days prior to initial administration Failure to recover from toxicity and/or complications of previous interventions to nCI-CTCAE ≤1 The half-life of CYP3A4 suppressor, moderate inhibitor or strong inducer or moderate inducer is less than 3 or less than 14 days from the date of first drug use, and the shorter is selected Received systemic immunosuppressant therapy within 14 days prior to the first study Subjects with known or suspected interstitial pneumonia In the first study, failure to swallow, chronic diarrhea, gastroenteritis, intestinal obstruction, gastrointestinal perforation, postgastrectomy, or colitis, or other medical conditions or special conditions affecting drug administration and absorption occurred within 28 days prior to administration Presence of any active, known or suspected autoimmune disease Have poorly controlled or severe cardiovascular disease Previous or concurrent malignancy Subjects who developed a severe infection within 28 days prior to the first dose Active hepatitis B There were active tuberculosis patients within 1 year before enrollment There is a history of immunodeficiency Live attenuated vaccine was administered within 28 days prior to initial study administration or is expected to be administered during study treatment Subjects who are participating in another clinical study or who have had their first dose less than 4 weeks since the end of the previous clinical study (last dose) or 5 half-lives of the study drug, whichever is shorter Major surgery other than diagnosis or biopsy was performed within 28 days prior to initial administration People who are known to be allergic to sir-A1811, pyrrolitinib, or any of the components of SIR-1316 History of severe allergic reactions to other monoclonal antibody/fusion protein drugs Female subjects who are pregnant, breast-feeding, or planning to become pregnant during the study Uncontrolled mental illness and other conditions known to affect the completion of the study process, such as alcohol, drug or substance abuse and detention Any other conditions that, in the investigator's judgment, may increase the risk of study participation, interfere with study results, or make study participation unsuitable

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: Single Group Assignment
Interventional Model Description: An open, multicenter, dose-increasing/investigational Phase IB/II clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811 combined with Pyrotinib/SHR-A1811 combined with SHR-1316<br> | Drug: SHR-A1811 & Pyrotinib/SHR-A1811 & SHR-1316<br>* Drug: SHR-A1811 & Pyrotinib SHR-A1811： intravenous Pyrotinib：oral Drug: SHR-A1811 & SHR-1316 SHR-A1811： intravenous SHR-1316： intravenous<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) main study endpoint) |  | 21 days after the first administration of each subject | 
| AE(Phase I (dose exploration phase) main study endpoint) |  | Two years after the last subject was enrolled in the group | 
| Incidence and severity of serious adverse events (SAE)(Phase I (dose exploration phase) main study endpoint) |  | Two years after the last subject was enrolled in the group | 
| Objective response rate(The main end points of the second stage (efficacy expansion stage)) |  | Two years after the last subject was enrolled in the group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxin binding antibody to shr-a1811（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Total antibody to shr-a1811（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of free toxin shr169265（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of pyrroltinib（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of SHR-1316（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Anti shr-a1811 antibody positive（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| The positive status of neutralizing antibody against shr-a1811（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Anti shr-1316 antibody positive（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| The positive status of neutralizing antibody against shr-1316（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Objective Response Rate（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Duration of response（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| Progression Free Survival（Phase I secondary endpoint） |  | Two years after the last subject was enrolled in the group | 
| AE（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Incidence and severity of serious adverse events (SAE)（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Toxin binding antibody to shr-a1811（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Total antibody to shr-a1811（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of free toxin shr169265（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of pyrroltinib（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Plasma concentration of SHR-1316（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Anti shr-a1811 antibody positive（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| The positive status of neutralizing antibody against shr-a1811（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Anti shr-1316 antibody positive（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| The positive status of neutralizing antibody against shr-1316（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Duration of response（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group | 
| Progression Free Survival（Phase II secondary study endpoint） |  | Two years after the last subject was enrolled in the group |