The Efficacy and Safety of IBI363 in Solid Tumors

NCT ID: NCT06081907

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-25
• Study Completion Date: 2028-09-01

Brief Summary

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.

Detailed Description

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. All the research data were collected follow the SAP.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IBI363 DL1

IBI363 + IBI325

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

IBI363 is based on the "3+3" model with a dose of 1 mg/kg Q3W. IBI325, 20 mg/kg Q3W.

IBI363 DL2

IBI363 + IBI325

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

IBI363 is based on the "3+3" model with a dose of 1.5 mg/kg Q3W. IBI325, 20 mg/kg Q3W.

IBI363 DL3

IBI363 + Lenvatinib

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

IBI363 is based on the "3+3" model with a dose of 600 μg/kg Q2W. Lenvatinib, 8mg QD.

IBI363 DL4

IBI363 + Lenvatinib

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

IBI363 is based on the "3+3" model with a dose of 1000 μg/kg Q2W. Lenvatinib, 8mg QD.

IBI363 DL5

Patients with histopathologically confirmed advanced melanoma, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL6

Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL7

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.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL8

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.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL9

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.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL10

Patients with histological or cytological confirmation of advanced NSCLC who harboring EGFR mutation and failed standard treatment.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

IBI363 DL11

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.

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

Interventions

IBI363

IBI363 is based on the "3+3" model with a dose of 1 mg/kg Q3W. IBI325, 20 mg/kg Q3W.

Intervention Type: DRUG

IBI363

IBI363 is based on the "3+3" model with a dose of 1.5 mg/kg Q3W. IBI325, 20 mg/kg Q3W.

Intervention Type: DRUG

IBI363

IBI363 is based on the "3+3" model with a dose of 600 μg/kg Q2W. Lenvatinib, 8mg QD.

Intervention Type: DRUG

IBI363

IBI363 is based on the "3+3" model with a dose of 1000 μg/kg Q2W. Lenvatinib, 8mg QD.

Intervention Type: DRUG

IBI363

The recommended dosages for IBI363, IBI325, and Lenvatinib 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).

Intervention Type: DRUG

Other Intervention Names

IBI325; IBI325; Lenvatinib; Lenvatinib

Eligibility Criteria

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:

1. Requiring medical intervention due to ventricular arrhythmias or other uncontrolled arrhythmias, such as treatment with anti-arrhythmic drugs.

2. Severe conduction disturbances (e.g., third-degree atrioventricular block).

3. HR-corrected QT interval (QTc interval, calculated using the Fridericia method) ≥480 ms.

4. Uncontrolled hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy.

5. A history of myocarditis.

6. Symptomatic congestive heart failure (New York Heart Association functional classes II-IV) or cardiac ultrasound findings indicating left ventricular ejection fraction (LVEF) <50%.

7. 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.

8. 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

Hunan Province Tumor Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongchang Zhang

Professor, Deputy Director of Thoracic Oncology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yongchang Zhang

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Nong Yang

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Xiang Chen

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Hong Liu

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Locations

Yongchang Zhang

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yongchang Zhang, MD

Role: CONTACT

zhangyongchang@csu.edu.cn

+8613873123436 ext. 7+861383123436

Nong Yang, MD

Role: CONTACT

yangnong0217@163.com

+8613873123436

Facility Contacts

Yongchang Yongchang Zhang, MD

Role: primary

zhangyongchang@csu.edu.cn

+8613873123436 ext. +8613873123436

Other Identifiers

IBI-363

Identifier Type: -

Identifier Source: org_study_id