Phase Ib/II Study of Almonertinib Combined With SHR-1701 in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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To evaluate the tolerability, safety, pharmacokinetic characteristics and immunogenicity of Almonertinib combined with SHR-1701 in relapsed or advanced NSCLC To evaluate the efficacy of Almonertinib combined with SHR-1701 in the first-line treatment of relapsed or advanced NSCLC

Official Title
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An Open-label, Multicenter Phase Ib/II Clinical Study of Almonertinib Combined With SHR-1701 or Other Innovative Drugs in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer With EGFR Mutation

Conditions
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Relapsed or Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Almonertinib combined with SHR-1701
* Drug: Almonertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients voluntarily joined the study and signed informed consent Age 18 75 years old, both male and female Advanced NSCLC diagnosed by histology or cytology, or recurrent NSCLC after radical treatment such as surgery, radiotherapy, chemoradiotherapy At least one measurable lesion based on RECIST v1.1 criteria ECOG PS score: 0-1 Have a life expectancy of at least 3 months Fertile women must have a negative serum pregnancy test within 3 days before the first dose and must be non-lactating Exclusion Criteria: Untreated Brain metastases with clinical symptoms; Or accompanied by meningeal metastasis, spinal cord compression，etc. Uncontrolled pleural, pericardial, or abdominal effusion with clinical symptoms Suffering from other malignant tumors in the past 3 years or at the same time Presence of any active or known autoimmune disease Subjects who had been systematically treated with corticosteroids (>10 mg/ day of prednisone or other equivalent hormone) or other immunosuppressive agents within 2 weeks prior to the first dose (randomization) Any severe or uncontrolled ocular lesions that, in the judgment of the investigator, may increase the subject's safety risk Have clinical symptoms or diseases of the heart that are not well controlled Patients with hypertension who are not well controlled by antihypertensive medication Any bleeding event of grade 2 or more or hemoptysis (volume of hemoptysis ≥2ml in a single episode) occurring within 2 weeks before the first dose (randomization); Clinically significant bleeding symptoms or definite bleeding tendency before the first medication (randomization) Have known history of serious infections within 1 month prior to the first dose(randomization), including but not limited to infectious complications that require hospitalization, bacteremia, and severe pneumonia; use antibiotics within 1 week prior to the first dose(randomization); have any active infections requiring intravenous systemic therapy, or have a fever > 38.5°C of unknown cause before the first dose(randomization). Have active or prior documented interstitial pneumonia/interstitial lung disease or pneumonitis that requires glucocorticoid treatment (e.g., radiation pneumonitis); Have active pneumonia at present Have active pulmonary tuberculosis. Have known history of human immunodeficiency virus (HIV) seropositive status or acquired immunodeficiency syndrome (AIDS). Have known active hepatitis B or C. Had received lung radiation therapy within 6 months before the first dose (randomization); Had received major surgical treatment (except diagnostic surgery), systemic chemotherapy, immunotherapy, or other investigational drugs within 4 weeks prior to the first medication (randomization); Received palliative radiotherapy within 2 weeks before the first dose (randomization); Oral administration of molecular targeted drugs, less than 5 half-lives before discontinuation of the drug to the first dose (randomization); Failure to recover from toxicity and/or complications of previous interventions to NCI-CTC AE grade≤1

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: Factorial Assignment
Interventional Model Description: This study is a multicenter, open-label, dose-exploring, and efficacy expansion phase Ib/II study. The first phase explored two doses of SHR-1701 plus fixed dose of almonertinib to confirm RP2D. The second phase is for efficacy expansion through randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Almonertinib combined with SHR-1701<br> | Drug: Almonertinib combined with SHR-1701<br>* Phase Ⅰb/Phase Ⅱ： SHR-1701: injection, intravenous infusion Almonertinib: tablets, oral<br>|
| Placebo Comparator: Almonertinib<br> | Drug: Almonertinib<br>* Phase Ⅱ: Almonertinib: tablets, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity （Phase Ib） |  | 21 days after the first dose | 
| The incidence and severity of ≥ grade 3 treatment-related adverse events (TRAE) and serious adverse events (TRSAE) in the combination of two drugs （Phase Ib） |  | from the time when all informed subjects signed the informed consent to the end of the safety follow-up period | 
| PFS rate at 12 months | Progression-Free-Survival, defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. | 12 months after the first medication for the last subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events and Serious Adverse Events |  | up to 3 years | 
| Proportion of dose pauses, dose downgrades and dose terminations due to study-drug related toxicities during the trial |  | up to 3 years | 
| ORR |  | up to 3 years | 
| DCR | Disease Control Rate, determined using RECIST v1.1 criteria | up to 3 years | 
| DoR | Duration of Response, determined using RECIST v1.1 criteria | up to 3 years | 
| DepOR | Depth of tumor remission, determined using RECIST v1.1 criteria | up to 3 years | 
| PFS | Progression-Free-Survival, determined using RECIST v1.1 criteria | up to 3 years | 
| OS | OS is the time interval from the date of randomization to death due to any reason or lost of follow-up | up to 5 years |