The Efficacy and Safety of IBI363 in Solid Tumors.

Study Overview
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Brief Summary
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The study is a prospective multi-cohort clinical study. The study is divided into two phases, Phase Ia and Phase Ib. In Phase Ia, a dose escalation portion was conducted using a 3+3 dose-escalation design, with a preference for enrolling subjects with advanced non-small cell lung cancer and melanoma. Phase Ib represents the cohort expansion phase, comprising seven cohorts.

Official Title
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A Prospective, Multi-cohort Study on Efficacy and Safety of IBI363 for Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: IBI363
* Drug: IBI363
* Drug: IBI363
* Drug: IBI363
* Drug: IBI363


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; Phase Ia: Enrollment priority is given to subjects with advanced non-small cell lung cancer and melanoma. Phase Ib: This study comprises seven cohorts, including: Cohort A: Patients with histopathologically confirmed advanced melanoma, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC. Cohort B: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC. Cohort C: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was disease stabilization for less than 6 months or disease progression. Cohort D: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was partial response or complete response lasting more than 6 months. Cohort E: Patients with histologically confirmed advanced NSCLC, who have undergone NGS testing confirming the presence of an ALK fusion mutation and have previously failed standard treatment. Cohort F: Patients with histological or cytological confirmation of advanced NSCLC who harboring EGFR mutation and failed standard treatment. Cohort G: Patients with histological or cytological confirmation of advanced NSCLC and failed standard treatment with rare mutations, including but not limited to ROS1, BRAF V600E, METex14 skipping, HER2, NTRK, and RET fusion. Tumor assessment according to RECIST v1.1, at least one measurable lesion. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: 1. Known history of seizures, active central nervous system metastasis, spinal cord compression, carcinomatous meningitis, history of meningeal metastasis, and newly diagnosed brain metastasis or meningeal metastasis. a) Subjects who have previously received treatment for central nervous system metastases must meet all of the following criteria to be eligible for this study: Completed treatment for central nervous system metastases (e.g., whole-brain radiation therapy, stereotactic radiosurgery, or equivalent treatment) at least 14 days before the first dose of the investigational drug. Post-treatment repeat imaging confirmed no evidence of new brain metastases or enlargement of existing brain metastatic lesions (with an interval of ≥4 weeks and using the same imaging technique as the pre-treatment head imaging). No requirement for steroid treatment and stable symptoms for at least 14 days before the first dose of the investigational drug. b) Subjects who have not previously received treatment for central nervous system metastases must meet all of the following criteria to be eligible for this study: No symptoms related to central nervous system metastases. Investigator assessment that immediate treatment for central nervous system metastases is not required. A maximum of three central nervous system metastatic lesions, with each lesion having a maximum diameter of ≤5 mm. 2. Significant cardiovascular and cerebrovascular diseases, including: Requiring medical intervention due to ventricular arrhythmias or other uncontrolled arrhythmias, such as treatment with anti-arrhythmic drugs. Severe conduction disturbances (e.g., third-degree atrioventricular block). HR-corrected QT interval (QTc interval, calculated using the Fridericia method) ≥480 ms. Uncontrolled hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy. A history of myocarditis. Symptomatic congestive heart failure (New York Heart Association functional classes II-IV) or cardiac ultrasound findings indicating left ventricular ejection fraction (LVEF) <50%. Any arterial thrombosis, embolism, or ischemic event (e.g., myocardial infarction, unstable angina, cerebrovascular accident) within 6 months prior to the first dose of the investigational drug. History of deep venous thrombosis or any other serious thromboembolic event within the 3 months before enrollment (implantable venous access port or catheter-related thrombosis, or superficial venous thrombosis are not considered serious thromboembolic events).

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI363 DL1<br>IBI363 | Drug: IBI363<br>* IBI363 is based on the 3+3 model with a dose of 1 mg/kg Q3W.<br>|
| Experimental: IBI363 DL2<br>IBI363 | Drug: IBI363<br>* IBI363 is based on the 3+3 model with a dose of 1.5 mg/kg Q3W.<br>|
| Experimental: IBI363 DL3<br>IBI363 | Drug: IBI363<br>* IBI363 is based on the 3+3 model with a dose of 600 μg/kg Q2W.<br>|
| Experimental: IBI363 DL4<br>IBI363 | Drug: IBI363<br>* IBI363 is based on the 3+3 model with a dose of 1000 μg/kg Q2W<br>|
| Experimental: IBI363 DL5<br>Patients with histopathologically confirmed advanced melanoma, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL6<br>Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL7<br>Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was disease stabilization for less than 6 months or disease progression. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL8<br>Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was partial response or complete response lasting more than 6 months. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL9<br>Patients with histologically confirmed advanced NSCLC, who have undergone NGS testing confirming the presence of an ALK fusion mutation and have previously failed standard treatment. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL10<br>Patients with histological or cytological confirmation of advanced NSCLC who harboring EGFR mutation and failed standard treatment. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|
| Experimental: IBI363 DL11<br>Patients with histological or cytological confirmation of advanced NSCLC and failed standard treatment with rare mutations, including but not limited to ROS1, BRAF V600E, METex14 skipping, HER2, NTRK, and RET fusion. | Drug: IBI363<br>* The recommended dosages for IBI363, IBI325, and Erlotinib in Phase Ib will be determined based on a comprehensive assessment of safety, efficacy, and other data obtained from the safety introduction portions of both Phase Ia (Part A) and Phase Ib (Part B).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event | Number of participants experiencing clinical and laboratory adverse events (AEs) | Up to 90 days post last dose | 
| ORR | Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects | 1 year |