CT-95 in Advanced Cancers Associated With Mesothelin Expression

Phase 1

Recruiting

• Conditions: Mesothelin-Expressing Tumors; Epithelial Ovarian Cancer; Malignant Pleural Mesothelioma, Advanced; Malignant Peritoneal Mesothelioma, Advanced; Lung Adenocarcinoma Metastatic; Cholangiocarcinoma Advanced; Mesothelin-expressing Advanced Cancers; Mesothelin-positive Advanced Malignant Solid Tumors; Colorectal Cancer; Pancreatic Adenocarcinoma Advanced or Metastatic
• Interventions: Drug: CT-95

• Registration Number: NCT06756035
• Lead Sponsor: Context Therapeutics Inc.

Brief Summary

This is a Phase 1a/1b open-label, dose escalation study to evaluate the safety and efficacy of CT-95 (study drug), a humanized T cell engaging bispecific antibody targeting Mesothelin, in subjects with advanced solid tumors associated with Mesothelin expression.

Detailed Description

The Phase 1a Dose Escalation portion of the trial will enroll subjects in one of approximately 8 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 study in 2 dose optimization cohorts. Subjects will receive CT-95 as a single agent administered once weekly (QW) intravenously (IV) over a 4-week cycle.

The Phase 1b Dose Expansion portion will evaluate CT-95 in indication-specific expansion cohorts

Study Timeline

• Study First Submitted: 2024-12-18
• Study First Submitted QC: 2024-12-24
• Study First Posted: 2025-01-01
• Study Start: 2025-03-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-22
• Primary Completion: 2026-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CT-95	CT-95	Each dose cohort will have weekly dosing. Anticipate approximately 8 dose cohorts.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Context Investigational Site; 🇺🇸 San Antonio, Texas, United States