CT-95 in Advanced Cancers Associated With Mesothelin Expression

Phase 1a Dose Escalation: Participants with ovarian epithelial tumors, primary peritoneal or fallopian tube cancer (PROC), epithelioid mesothelioma, lung adenocarcinoma, pancreatic adenocarcinoma, colorectal cancer, cholangiocarcinoma, and gastric/GEJ adenocarcinomas will be enrolled in one of approximately 9 dose escalation cohorts to assess the safety and tolerability of CT-95, as well as determine the maximum tolerated dose (MTD) or other recommended dose(s) for expansion (RDE\[s\]) for further dose expansion cohorts.

Participants will receive CT-95 as a single agent administered once weekly (QW) intravenously (IV) over a 4-week cycle.

Phase 1b Dose Expansion: The RDE(s) of CT-95 determined in Phase 1a will be evaluated in 2-4 indication-specific expansion cohorts of up to 20 subjects each (i.e. up to 80 participants total). Different indications, dose levels, and/or schedules may be explored. The expansion doses and/or dosing schedules for Phase 1b will be determined by Sponsor in conjunction with SRC based upon all available safety, PK, PD, biomarker, and preliminary efficacy data from Phase 1a.

• CT-95 (Drug): MSLN bispecific antibody to be administered according to the dose and schedule of the assigned cohort until documentation of disease progression (or confirmed disease progression), unacceptable toxicity, or participant/physician decision.

Primary outcomes

• Determine the MTD or RD of CT-95 [Safety and Tolerability] [From date of first dose of CT-95 until 28 days following the first dose.]: The frequency of dose-limiting toxicities (DLTs) will be analyzed along with safety and tolerability measures to determine the MTD or RD of CT-95.
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [From date of first dose of CT-95 for approximately 6 months or until treatment discontinuation, whichever comes first.]: The frequency and severity of adverse events, serious adverse events, and adverse events of special interest will be analyzed.

Secondary outcomes

• Evaluate Response Rates [Anti-tumor Activity] [At 8-week intervals from the time of the first dose of CT-95 for approximately 6 months or until treatment discontinuation, whichever comes first]: Overall response rates will be calculated using RECIST 1.1 (and mRECIST for patients with mesothelioma) for CT-95.
• Evaluate Progression-free Survival [Anti-tumor Activity] [At 8-week intervals from the time of the first dose of CT-95 for approximately 6 months or until treatment discontinuation, whichever comes first.]: PFS will be summarized using RECIST 1.1 (and mRECIST for patients with mesothelioma) for CT-95.
• Evaluate Overall Survival [Survival] [From the time of the first dose of CT-95 until approximately two years post-first dose.]: Overall survival will be summarized for CT-95.
• Evaluate the Maximum Serum Concentration (Cmax) [Pharmacokinetics] [From date of first dose of CT-95 for 5 months or until treatment discontinuation, whichever comes first.]: Serum concentrations of CT-95 analyzed as a function of time relative to dosing will be calculated.
• Evaluate the Area Under the Curve (AUC) [Pharmacokinetics] [From date of first dose of CT-95 for 5 months or treatment discontinuation, whichever comes first.]: The AUC of CT-95 analyzed as a function of time relative to dosing will be calculated.
• Evaluate Anti-Drug Antibodies [Immunogenicity] [From date of first dose of CT-95 for 5 months or until treatment discontinuation, whichever comes first.]: Incidence and titer of ADAs will be evaluated.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* ECOG 0 or 1
* Subjects with evaluable disease per RECIST 1.1 or mRECIST
* Subjects with adequate organ function.
* Subjects with advanced cancers associated with mesothelin expression

Exclusion Criteria:

* Uncontrolled significant active infection or any medical or other condition that in opinion of the investigator would preclude the subject's participation in the study.
* Prior treatment with MSLN-targeted CD3 or chimeric antigen receptor T cell (CAR-T) therapy
* Concurrent participation in another investigational clinical trial.
* Evidence of leptomeningeal disease

• Karen Chagin, MD, Study director, Context Therapeutics Inc.