CT-95 in Advanced Cancers Associated With Mesothelin Expression

Phase 1a/1b Study of CT-95 in Advanced Cancers Associated With Mesothelin Expression

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Epithelial Ovarian Cancer; Cholangiocarcinoma Non-resectable; Lung Adenocarcinoma Metastatic; Malignant Pleural Mesothelioma, Advanced; Cholangiocarcinoma Advanced; Pancreatic Adenocarcinoma Advanced or Metastatic; Mesothelin-positive Advanced Malignant Solid Tumors; Mesothelin-expressing Advanced Cancers; Malignant Peritoneal Mesothelioma, Advanced; Mesothelin-Expressing Tumors
• Intervention / Treatment: Drug: CT-95

Detailed Description

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
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Context Clinical Development; Phone Number: 267-225-7416; Email: cntx-ct95-101@contexttherapeutics.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Context Investigational Site
      • Contact: Front Desk; Phone Number: 720-754-2610; Email: CANN.DDUDenverGeneral@SarahCannon.com
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Context Investigational Site
      • Contact: Cancer Clinical Trials; Phone Number: 773-702-6233; Email: Cancerclinicaltrials@bsd.uchicago.edu
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Context Investigational Site
      • Contact: Ashley Spagnuolo; Phone Number: 616-954-5552; Email: ashley.spagnuolo@startresearch.com
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Context Investigational Site
      • Contact: Oncology Clinical Research Referral Office; Phone Number: 551-996-1777; Email: OncologyResearchReferral@hmhn.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Andrea Standish; Phone Number: 215-662-2419; Email: andrea.standish@pennmedicine.upenn.edu
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Context Investigational Site
      • Contact: Ask Phase1; Phone Number: 215-586-0199; Email: AskPhase1@jefferson.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Context Investigational Site
      • Contact: Sarah Cannon Research Institute; Phone Number: 844-482-4812
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Context Investigational Site
      • Contact: Isabel Jimenez; Phone Number: 210-593-5265; Email: isabel.jimenez@startresearch.com
      • Contact: Christina Santana; Email: csantana@startresearch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT-95; Phase 1a: Dose Escalation - each dose cohort will assess toxicity 28 days following the first dose of CT95 anticipate a total of 8 dose cohorts. Phase 1b: Dose Expansion - approximately 80 participants will be evaluated in 2-4 indication-specific expansion cohorts.	Drug: CT-95; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine 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.	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.	From date of first dose of CT-95 for approximately 6 months or until treatment discontinuation, whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	From date of first dose of CT-95 for 5 months or until treatment discontinuation, whichever comes first.

Collaborators and Investigators

• Sponsor: Context Therapeutics Inc.
• Investigators: Study Director: Karen Chagin, MD, Context Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): January 1, 2025

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Phase 1 Dose Escalation Study; CT-95; Advanced, recurrent cancers; Unresectable, metastatic cancers; Cancers associated with mesothelin expression
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Carcinoma; Ovarian Neoplasms; Pathological Conditions, Signs and Symptoms; Mesothelioma; Carcinoma, Ovarian Epithelial; Mesothelioma, Malignant; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: CNTX-CT95-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No