Efficacy and Biomarker Explanation of IBI-323 + Bevacizumab Plus Platinum Based Chemotherapy on ALK-Rearranged NSCLC

Study Overview
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Brief Summary
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This study aimed to explore the efficacy and biomarker explanation of IBI-323 combined with bevacizumab plus platinum based chemotherapy on ALK-rearranged non-small cell lung cancer who failed from first line Alectinib.

Official Title
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Efficacy and Biomarker Explanation of IBI-323 Combined With Bevacizumab Plus Platinum Based Chemotherapy on ALK-Rearranged Non-Small Cell Lung Cancer Who Failed From First Line Alectinib

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: IBI-323 combined with bevacizumab plus Platinum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign written informed consent before implementing any trial-related procedures; Age ≥18 years old and ≤75 years old. No limit on the gender. Patients diagnosed with Lung Adenocarcinoma ALK-Rearranged Stage IIIA-IV by pathology. Patients who failed from first line Alectinib with stable brain metastasis included (Radiotherapy treated Oligo-metastasis). According to the Solid Tumor Efficacy Evaluation Criteria (RECIST V1.1), at least one lesion can be measured on imaging. Lesions located in the field of previous radiation therapy may be considered measurable if progression is demonstrated. ECOG score 0-1 points. Exclusion Criteria: Patients with contraindication of chemotherapy Pregnant or breast feeding women. Participate in another interventional clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study. Participants are known to have had previous severe allergic reactions to other monoclonal antibodies or to any of the components of the IBI323 preparation, and severe allergies to bevacizumab, pemetrexed, cisplatin, and carboplatin. Previous systematic anti-tumor therapy for advanced non-squamous NSCLC other than ALK-TKI (including cytotoxic chemotherapy in combination with radiotherapy). Previous use of anti-PD-1 anti-PD-L1 anti-programmed death receptor ligand 2(PD-L2) or anti-cytotoxic T-lymphocyte-associated antigen 4(CTLA-4) drugs or any other drugs that act on T-cell co-stimulation or checkpoint pathways (such as OX40 CD137 LAG3, etc.). Radical radiation therapy within 28 days prior to the first dose, or palliative radiation therapy within 14 days prior to the first dose. Received ALK-TKI treatment within 2 weeks prior to the first administration of the study drug

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>patients with only 3'ALK confirmed by NGS | Drug: IBI-323 combined with bevacizumab plus Platinum<br>* IBI-323 (30 mg/kg) ccombined with bevacizumab (15 mg/kg) plus platinum based chemotherapy ivgtt, every 21 days until disease progression<br>|
| Experimental: Cohort B<br>patients with 3'ALK with retention of 5'ALK | Drug: IBI-323 combined with bevacizumab plus Platinum<br>* IBI-323 (30 mg/kg) ccombined with bevacizumab (15 mg/kg) plus platinum based chemotherapy ivgtt, every 21 days until disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Defined as the time from the start of treatment to the death of the subject due to any cause. | 1 year | 
| DCR | Disease control rates were assessed according to RECIST V1.1 | 1 year |