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

• Sponsor: Northern Biologics Inc.
• Information provided by (Responsible Party): Northern Biologics Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors; Pancreatic Cancer; Non Small Cell Lung Cancer; Ovarian Cancer	Biological: MSC-1	Phase 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 130 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-Label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 11, 2018
• Estimated Primary Completion Date: December 31, 2019
• Estimated Study Completion Date: July 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Confirm safest dose of MSC-1 for further study [ Time Frame: Patients will be evaluated for approximately 6 months or until disease progression ]
   Assessment of adverse events
2. Characterize the PK of MSC-1 [ Time Frame: 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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

HonorHealth

Scottsdale, Arizona, United States, 85258

United States, Michigan

START MidWest

Grand Rapids, Michigan, United States, 49546

United States, New Jersey

Memorial Sloan Kettering Cancer Center- Monmouth

Middletown, New Jersey, United States, 07748

United States, New York

Memorial Sloan Kettering Cancer Center- Westchester

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Canada, Ontario

Princess Margaret Cancer Center

Toronto, Ontario, Canada, M5G 1Z5

Spain

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08035

Sponsors and Collaborators

Northern Biologics Inc.

Investigators

• Study Director: Robert Wasserman, MD; Northern Biologics Inc.

More Information

Additional Information:

Sponsor Website 

• Responsible Party: Northern Biologics Inc.
• ClinicalTrials.gov Identifier: NCT03490669 History of Changes
• Other Study ID Numbers: MSC-1-101
• First Posted: April 6, 2018
• Last Update Posted: May 23, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases