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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors, Pancreatic Cancer, Non Small Cell Lung Cancer, Ovarian Cancer

Intervention / Treatment
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* Biological: MSC-1


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

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 |