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

Phase 1

Completed

• Conditions: Advanced Solid Tumors; Pancreatic Cancer; Non Small Cell Lung Cancer; Ovarian Cancer
• Interventions: Biological: MSC-1

• Registration Number: NCT03490669
• Lead Sponsor: AstraZeneca

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-02-07
• Study First Submitted QC: 2018-03-30
• Study First Posted: 2018-04-06
• Study Start: 2018-05-21
• Primary Completion: 2019-09-23
• Study Completion: 2019-09-23
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-04
• Last Update Posted: 2024-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Expansion	MSC-1	MSC-1 treatment at the recommended Phase 2 dose once every 3 weeks
Dose Escalation	MSC-1	Multiple dose levels of MSC-1 treatment once every 3 weeks

Primary Outcome Measures

Name	Time	Method
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	Patients will be evaluated for approximately 6 months or until disease progression	Assessment of frequency \& severity of adverse events
Assess the preliminary anti-tumor activity of MSC-1 monotherapy	Patients will be evaluated for approximately 6 months or until disease progression	Determine objective response rate (ORR)

Secondary Outcome Measures

Name	Time	Method
Confirm safest dose of MSC-1 for further study	Patients will be evaluated for approximately 6 months or until disease progression	Assessment of adverse events
Characterize the PK 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	Serum levels of MSC-1

Trial Locations

Locations (7)

Princess Margaret Cancer Center; 🇨🇦 Toronto, Ontario, Canada

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center- Westchester; 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Cancer Center- Monmouth; 🇺🇸 Middletown, New Jersey, United States

HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

START MidWest; 🇺🇸 Grand Rapids, Michigan, United States