A Phase 1, Open-label, Multicenter, Dose Escalation Study of IBI363 (PD1-IL2m) in Subjects With Advanced Solid Malignancies or Lymphomas

This is a Phase 1, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD), and the RP2D of sequential doses of IBI363 (study drug) in subjects with advanced, refractory solid malignancies or lymphomas.

Study Overview

• Status: Recruiting
• Conditions: Solid Malignancies or Lymphomas
• Intervention / Treatment: Biological: IBI363

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Min Luo; Phone Number: 00861087412310; Email: min.luo@innoventbio.com

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Southern Medical Day Care Centre
      • Contact: Morteza Aghmesheh; Phone Number: 0061242225200; Email: Morteza.Aghmesheh@health.nsw.gov.au

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female subjects, ≥ 18 years
2. Subjects with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; subjects with documented lymphomas
3. Subjects with a malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor
4. Subjects who are refractory to or intolerant to existing therapy(ies) known to provide clinical benefit Note: Subjects may have received and failed prior therapy with a PD-1/PD-L1 inhibitor and be considered eligible for this trial.
5. Subjects with measurable or non-measurable disease according to RECIST v1.1 or standard criteria for lymphoma (Lugano 2014)
6. Subjects, both male and female, who are either not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug
7. Subjects with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol

Exclusion Criteria:

1. Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) or fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
2. 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.

3. 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.
   • Active uncontrolled bleeding or a known bleeding diathesis.

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
Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)	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 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 hematology parameters	Blood samples will be collected to evaluate hemoglobin, mean corpuscular volume (MCV), white blood cell (WBC) count, platelets, 5-part differential white cell count, mean platelet volume 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
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	28 days during the first 4-week cycle

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
clearance (CL)	PK parameters to be evaluated for IBI363 including area under the curve (AUC) will be determined when appropriate.	Up to 2 years
half-life (t1/2) of IBI363	PK parameters to be evaluated for IBI363 including volume of distribution (V) 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
6-month and 1-year PFS rate per RECIST v1.1 for subjects with solid tumors, and per Lugano 2014 for subjects with lymphomas	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
survival rates (6-month and 1-year)	To evaluate the preliminary antitumor activity of IBI363	Up to 2 years
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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Principal Investigator: Morteza Aghmesheh, Southern Medical Day Care Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2022
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): August 31, 2024

Study Registration Dates

• First Submitted: January 9, 2022
• First Submitted That Met QC Criteria: March 13, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 4, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms; Lymphoma
• Other Study ID Numbers: CIBI363A101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes