A Phase I Study of MSB2311 in Advanced Solid Tumors

First-in-human, Open-label, Phase 1 Dose-Escalation Study of MSB2311, A Humanized Anti-PD-L1 Monoclonal Antibody in Subjects With Advanced Solid Tumors

This is a phase I study to determine the safety and toxicity, PK/PD, immunogenicity, biomarkers, anti-tumor activity and establish a preliminary recommended Phase 2 dose (RP2D) in subjects with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: 3 mg/kg Q3W MSB2311 Injection; Drug: 10 mg/kg Q3W MSB2311 Injection; Drug: 20 mg/kg Q3W MSB2311 Injection; Drug: 10 mg/kg Q2W MSB2311 Injection

Detailed Description

This is a first-in-human (FIH), open-label, Phase 1 dose-Escalation Study of MSB2311, a humanized anti-PD-L1 monoclonal antibody, in subjects with advanced solid tumors. Qualified subjects will be enrolled to receive their assigned dose regimen of MSB2311 until disease progression or intolerable toxicity, withdrawal of consent, or end of study, whichever occurs first. The maximum treatment duration is 2 years. During the study, subjects will be evaluated for safety and toxicity, PK/PD, immunogenicity, biomarkers, and anti-tumor activity of MSB2311.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Able to understand and willing to sign the ICF.
• Male or female subject ≥ 18 years.
• Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors that are refractory to standard therapy, or for which no standard therapy exists.
• Subject has measurable disease per RECIST v1.1.
• ECOG Performance Status 0 to 1
• Subjects with life expectancy of ≥ 3 month
• No herbal/alternative medications prior to the first dose
• Must have adequate hematological, hepatic and renal function as defined in the protocol.
• Prior anti-tumor therapies of different kinds must have stopped before the first dose as defined by protocol
• Effective contraception for both male and female subjects if the risk of conception exists

Exclusion Criteria:

• Pregnant or nursing females.
• Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v4. 03, with exception of the residual hair loss;
• Received a biologic G-CSF, GM-CSF or erythropoietin within 14 days prior to the first dose of study drug;
• Subjects who had prior treatment with an anti-PD-L1 product
• History of documented autoimmune disease except for autoimmune hypothyroidism and well-controlled Type 1 diabetes mellitus.
• W/o autoimmune condition requiring systemic treatment with immunosuppressive medications within 14 days before the planned first dose of study drug.
• Primacy central nervous system (CNS) malignancy or symptomatic CNS metastases are not allowed, with exceptions defined in protocol.
• Major surgery within the 28-days from the screening
• Subjects with idiopathic pulmonary fibrosis or unresolved active or chronic inflammatory pulmonary disease are excluded.
• History of human immunodeficiency virus (HIV) infection, active hepatitis B or C. HBV carriers
• History of primary immunodeficiency, stem cell or organ transplant, or previous clinical diagnosis of tuberculosis disease.
• Clinically significant acute infections 4 weeks and any infection 2 weeks prior to the first dose administration.
• Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a history of any significant drug allergy
• Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who had to discontinue prior anti-PD-1 treatment due to irAEs of any grade.
• Severe or uncontrolled cardiac disease requiring treatment as defined in protocol
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, might impair the subject's benefit from the trial treatment
• Known history of hypersensitivity to any components of the MSB2311 product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 mg/kg (Q3W) MSB2311 Injection; MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 3 mg/kg.	Drug: 3 mg/kg Q3W MSB2311 Injection; An intravenous infusion with concentration from 3 mg/kg (Q3W); Other Names: 3 mg/kg Q3W MSB2311
Experimental: 10 mg/kg (Q3W) MSB2311 Injection; MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 10 mg/kg.	Drug: 10 mg/kg Q3W MSB2311 Injection; An intravenous infusion with concentration from 10 mg/kg (Q3W); Other Names: 10 mg/kg Q3W MSB2311
Experimental: 20 mg/kg (Q3W) MSB2311 Injection; MSB2311 will be administered as an IV infusion once every 3 weeks (Q3W) starting at 20 mg/kg.	Drug: 20 mg/kg Q3W MSB2311 Injection; An intravenous infusion with concentration from 20 mg/kg (Q3W); Other Names: 20 mg/kg Q3W MSB2311
Experimental: 10 mg/kg (Q2W) MSB2311 Injection; MSB2311 will be administered as an IV infusion once every 2weeks (Q2W) starting at 10 mg/kg.	Drug: 10 mg/kg Q2W MSB2311 Injection; An intravenous infusion with concentration from 10 mg/kg (Q2W); Other Names: 10 mg/kg Q2W MSB2311

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of MSB2311	Measured by number adverse events that are related to treatment	Up to 90 days following the last dose
Maximum tolerated dose or recommended phase 2 dose	Measured by number of subjects experiencing DLT in each escalation cohort	Up to 90 days following the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) for MSB2311		Up to 30 days following the last dose
Peak Plasma concentration (Cmax)for MSB2311	Incidence and quantity of anti-drug antibodies	Up to 30 days following the last dose
Volume of plasma from which MSB2311 is completely removed per unit time (CL)		Up to 30 days following the last dose
The incidence of subjects generating anti-drug antibody		Up to 30 days following the last dose
Objective response rate (ORR) as measured by RESISTv1.1		Up to 30 days following the last dose
Duration of response (DOR) as measured by RESISTv1.1		Up to 30 days following the last dose
Progression-free survival (PFS) as measured by RESISTv1.1		Up to 30 days following the last dose
Best overall response as measured by RESISTv1.1		Up to 30 days following the last dose
Overall survival (OS) as measured by RESISTv1.1		Up to 30 days following the last dose
Elimination half-life and apparent plasma terminal phase elimination rate constant (t1/2 ) of MSB2311		Up to 30 days following the last dose

Collaborators and Investigators

• Sponsor: Suzhou Transcenta Therapeutics Co., Ltd.
• Investigators: Study Director: Yonggang Wu, MD, Suzhou Transcenta Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 6, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MSB2311-CSP-001

Drug and device information, study documents

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