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

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.

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