Study to Evaluate Safety, PK, PD, Immunogenicity & Antitumor Activity of MSC-1 in Patients With Adv Solid Tumors

A Phase 1 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MSC-1 in Patients With Advanced Solid Tumors

This is a 2-part study to evaluate the safety and antitumor activity of MSC-1. MSC-1 is a first-in-class, humanized monoclonal antibody (IgG1) which binds to the immunosuppressive human cytokine Leukemia Inhibitory Factor (LIF), and is intended to treat adult patients with Advanced Solid Tumors.

In part 1, multiple dose levels of MSC-1 in patients with advanced solid tumors will be studied to determine the recommended dose for further evaluation of safety and efficacy in Part 2.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer; Ovarian Cancer; Non Small Cell Lung Cancer; Advanced Solid Tumors
• Intervention / Treatment: Biological: MSC-1

Detailed Description

MSC-1 is a first-in-class, humanized monoclonal antibody (IgG1) which binds to the immunosuppressive human cytokine Leukemia Inhibitory Factor (LIF), and is intended to treat adult patients with advanced solid tumors. LIF is a pleiotropic cytokine involved in many physiological and pathological processes including the promotion of an immunosuppressive environment. In cancer, it is hypothesized that LIF expressing malignancies co-opt this activity, creating an immunosuppressive tumor microenvironment as well as promoting the activity of cancer-initiating cell(s) (CICs). LIF is highly expressed in a subset of tumors across multiple solid tumor types.

During dose escalation, patients with advanced solid tumors will be treated with MSC-1 with the primary objective of determining the safety and tolerability of MSC-1 and defining an appropriate dose for further evaluation in dose expansion. MSC-1 will be administered intravenously (IV) until disease progression, unmanageable toxicity, withdrawal of consent or study termination.

In dose expansion, up to 4 parallel cohorts of patients with LIF-High tumors (NSCLC, Ovarian Cancer, Pancreatic Cancer), and a cohort of mixed solid tumors (referred to as the "basket cohort"), may be treated at the recommended expansion dose to further characterize the safety, tolerability, PK, PD and anti-tumor activity of MSC-1.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Cancer Center- Monmouth
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center- Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (All patients):

• Confirmed Advanced Unresectable Solid Tumor
• Measurable disease by RECIST 1.1 by CT or MRI
• Documented disease progression on or following last line of therapy
• Archival tumor sample for submission
• ECOG performance status 0 or 1
• Resolution of all acute, reversible toxic effects of prior therapy or surgical procedures to at least grade 1 (except alopecia and peripheral neuropathy to at least grade 2)
• Adequate organ function
• A limited number of patients enrolled in Dose Escalation may be required to agree to pre- and on-treatment tumor biopsies

Inclusion Criteria (Dose Expansion patients only)

• LIF- High NSCLC, Ovarian Cancer, or Pancreatic Cancer for the tumor-specific cohorts or Advanced Solid Tumor for the basket cohort as assessed by tumor tissue evaluation by IHC
• All patients enrolled in Dose Expansion must agree to undergo pre- and on-treatment tumor biopsies

Exclusion Criteria (All Patients):

• Systemic anti-cancer therapy within 4 weeks or 5 half-lives prior to study entry
• Previous or concurrent malignancy that could affect compliance with protocol or interpretation of results
• Clinically significant, unstable cardiovascular or pulmonary disease as specified in detail in the study protocol
• History of acquired or congenital immunodeficiency syndrome or receiving immunosuppressive therapy
• Uncontrolled infections or serologically positive HIV or hepatitis B or C infection
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or interfere with interpretation of study results

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Multiple dose levels of MSC-1 treatment once every 3 weeks	Biological: MSC-1; humanized monoclonal antibody for intravenous administration
Experimental: Dose Expansion; MSC-1 treatment at the recommended Phase 2 dose once every 3 weeks	Biological: MSC-1; humanized monoclonal antibody for intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the preliminary anti-tumor activity of MSC-1 monotherapy	Determine objective response rate (ORR)	Patients will be evaluated for approximately 6 months or until disease progression
Evaluate the safety and tolerability of MSC-1 and determine the recommended dose for MSC-1 monotherapy for further evaluation in the expansion part of the study	Assessment of frequency & severity of adverse events	Patients will be evaluated for approximately 6 months or until disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirm safest dose of MSC-1 for further study	Assessment of adverse events	Patients will be evaluated for approximately 6 months or until disease progression
Characterize the PK of MSC-1	Serum levels of MSC-1	Patients will be evaluated before and after each dose of MSC-1 for approximately 6 months or until disease progression. PK will be evaluated more frequently for the first 2 cycles of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Robert Wasserman, MD, Northern Biologics

Publications and helpful links

Helpful Links

• Sponsor Website
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): September 23, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: MSC-1-101; 2017-003320-79 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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