This is a Phase 1a/1b, first-in-human (FIH), open-label, multi-center dose escalation and expansion study of the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of single-agent CT-95 in subjects with advanced (recurrent, unresectable, or metastatic) cancers associated with MSLN 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
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.
Context Investigational Site
Denver, Colorado, United States
RECRUITINGContext Investigational Site
Chicago, Illinois, United States
RECRUITINGContext Investigational Site
Grand Rapids, Michigan, United States
RECRUITINGContext Investigational Site
Hackensack, New Jersey, United States
RECRUITINGUniversity of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGContext Investigational Site
Philadelphia, Pennsylvania, United States
RECRUITINGContext Investigational Site
Nashville, Tennessee, United States
RECRUITINGContext Investigational Site
San Antonio, Texas, United States
RECRUITINGContext Investigational Site
San Antonio, Texas, United States
RECRUITINGDetermine the MTD or RD of CT-95 [Safety and Tolerability]
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.
Time frame: From date of first dose of CT-95 until 28 days following the first dose.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The frequency and severity of adverse events, serious adverse events, and adverse events of special interest will be analyzed.
Time frame: From date of first dose of CT-95 for approximately 6 months or until treatment discontinuation, whichever comes first.
Evaluate Response Rates [Anti-tumor Activity]
Overall response rates will be calculated using RECIST 1.1 (and mRECIST for patients with mesothelioma) for CT-95.
Time frame: 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
Evaluate Progression-free Survival [Anti-tumor Activity]
PFS will be summarized using RECIST 1.1 (and mRECIST for patients with mesothelioma) for CT-95.
Time frame: 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.
Evaluate Overall Survival [Survival]
Overall survival will be summarized for CT-95.
Time frame: From the time of the first dose of CT-95 until approximately two years post-first dose.
Evaluate the Maximum Serum Concentration (Cmax) [Pharmacokinetics]
Serum concentrations of CT-95 analyzed as a function of time relative to dosing will be calculated.
Time frame: From date of first dose of CT-95 for 5 months or until treatment discontinuation, whichever comes first.
Evaluate the Area Under the Curve (AUC) [Pharmacokinetics]
The AUC of CT-95 analyzed as a function of time relative to dosing will be calculated.
Time frame: From date of first dose of CT-95 for 5 months or treatment discontinuation, whichever comes first.
Evaluate Anti-Drug Antibodies [Immunogenicity]
Incidence and titer of ADAs will be evaluated.
Time frame: From date of first dose of CT-95 for 5 months or until treatment discontinuation, whichever comes first.
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