Safety, Tolerability and Preliminary Efficacy of IBI363 in Subjects With Advanced Solid Tumors or Lymphoma

A Phase Ia/Ib Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of IBI363 in Subjects With Advanced Solid Tumors or Lymphoma

This study is an open-label, multicenter, phase Ia/Ib study. The study will evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced, relapsed or metastatic solid tumors or lymphoma, determine the maximum tolerated dose (MTD) or maximum administered dose (MAD), and thus determine the recommended phase 2 dose (RP2D).

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors or Lymphoma
• Intervention / Treatment: Biological: IBI363

Detailed Description

This study is an open-label, multicenter, phase Ia/Ib study. The study will evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced, relapsed or metastatic solid tumors or lymphoma, determine the maximum tolerated dose (MTD) or maximum administered dose (MAD), and thus determine the recommended phase 2 dose (RP2D). The phase Ia part consists of the dose escalation and PD marker exploration part. The phase Ib part consists of the dose expansion part.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiuzhi Yu; Phone Number: 0512-69566088; Email: xiuzhi.yu@innoventbio.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Tingbo Liang; Phone Number: 0571-87236688; Email: liangtingbo@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects, ≥ 18 years
2. Histologically or cytologically confirmed, unresectable locally advanced or metastatic solid tumors or lymphomas
3. Subjects who progressed or are intolerant to existing standard therapy or subjects without standard therapy Note: Subjects may have received and failed prior therapy with a PD-1/PD-L1 inhibitor and be considered eligible for this trial.
4. Subjects with at least one measurable lesion according to RECIST v1.1 for solid tumor or Lugano 2014 for lymphoma
5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
6. Expected survival time ≥ 3 months.

Exclusion Criteria:

1. Subjects with history of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
2. Subjects with active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to first administration of study drug unless adequately treated and considered by the Investigator to be stable.
3. Active uncontrolled bleeding or a known bleeding diathesis.
4. Subjects with massive pleural effusion or massive ascites.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IBI363; Single arm	Biological: IBI363; a mutated IL-2 cytokine fused to an anti-PD-1 antibody to combine IL-2 pathway stimulation with checkpoint blockade.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with abnormality in vital signs	Blood pressure, pulse, respiratory rate, and temperature will be assessed.	up to 90 days after the last administration
Number of participants with abnormality in clinical chemistry parameters	Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), bicarbonate, amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase and lipase.	up to 90 days after the last administration
Number of participants with abnormality in routine urinalysis parameters	Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen.	up to 90 days after the last administration
Number of participants with abnormality in ECG parameters	12-lead ECG will be obtained using an ECG machine. Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded.	up to 90 days after the last administration
Number of dose-limiting toxicity (DLT)	Incidence of dose-limiting toxicity (DLT) events	21 days during the first 3-week cycle
incidence of adverse enents (AE), serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)	AE is defined as an unexpected medical problem that happens during treatment with a drug or other therapy. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. A TEAE will be defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered. irAEs will be assessed.	up to 90 days after the last administration
Number of participants with abnormality in hematology parameters	Blood samples will be collected to evaluate hemoglobin, white blood cell (WBC) count, platelets and coagulation factors including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT)	up to 90 days after the last administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum concentration (Cmax)	PK parameters to be evaluated for IBI363 including maximum concentration (Cmax) will be determined when appropriate.	Up to 2 years
area under the curve (AUC)	PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.	Up to 2 years
Objective response rate (ORR)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
time to response (TTR)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
duration of response (DoR)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
disease control rate (DCR)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
progression-free survival (PFS)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
Overall survival (OS)	To evaluate the preliminary antitumor activity of IBI363	through study completion, an average of 1 year
The incidence of ADA and NAb of IBI363	Each subject will be tested for anti-drug (IBI363) antibody (ADA), and ADA-positive serum samples will continue to be tested for neutralizing antibodies (NAb).	Up to 2 years
clearance (CL)	PK parameters to be evaluated for IBI363 including clearance (CL) will be determined when appropriate.	Up to 2 years
half-life (t1/2) of IBI363	PK parameters to be evaluated for IBI363 including half-life (t1/2) will be determined when appropriate.	Up to 2 years
volume of distribution (V)	PK parameters to be evaluated for IBI363 including volume of distribution (V) will be determined when appropriate.	Up to 2 years
6-month and 1-year PFS rate	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
6-month and 1-year OS rate	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 24, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: CIBI363A102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No