CT-95 Phase 1 Trial Enrolls and Doses First Patient With MSLN+ Advanced Cancer

A medical illustration featuring cancer cells from a microscopic to macroscopic view, illuminated by neon lights to enhance visual clarity and focus: © Fay Melronna - stock.adobe.com

A phase 1 trial (NCT06756035) evaluating CT-95, a mesothelin (MSLN) x CD3 T-cell engaging bispecific antibody that targets mesothelin-expressing cancers, has dosed its first patient with a MSLN-expressing advanced solid tumor.¹

In this phase 1, open-label, dose-escalation and dose-expansion trial, investigators are evaluating CT-95’s safety and efficacy for the treatment of patients with MSLN-expressing advanced solid tumors, including ovarian, pancreatic, lung, and mesothelioma cancers. The estimated enrollment of the study is 50 patients.²

Initial results from the trial are expected to be released in mid-2026.¹

“Dosing of the first patient in our CT-95 phase 1 clinical trial represents another step forward in our mission to develop next generation precision immunotherapies for solid tumors,” said Martin Lehr, chief executive officer of Context, in the press release. “With both CT-95 and CTIM-76 now dosed in initial patients, we are advancing our clinical pipeline and expanding our leadership in T-cell engaging bispecific antibody therapies.”

CT-95 works to redirect T-cell–mediated lysis toward malignant cells that express MSLN, a membrane protein that is overexpressed in about 30% of cancers. This fully humanized bispecific T-cell engager has a moderate affinity, but high avidity for membrane-bound MSLN, and is currently being developed for advanced cancers that are associated with MSLN expression, including pancreatic, ovarian, mesothelioma, and other solid tumors.¹

In the dose-escalation and dose-expansion portions of the phase 1 trial evaluating CT-95, experts will assess its safety, tolerability, pharmacokinetics, and antitumor activity, including overall response rate (ORR), duration of response, and disease control rate.² In the dose-escalation portion of the trial, patients will be enrolled into 1 of approximately 8 dose escalation cohorts to assess CT-95’s safety and tolerability and to determine its maximum tolerated dose (MTD) or recommended dose.

CT-95 will be administered once a week for each cycle that consists of 28 days. Patients will continue to receive treatment until documentation of disease progression, unacceptable toxicity, or subject/physician decision.

Patients with an ECOG performance status of 0 or 1, evaluable disease per RECIST 1.1 or mRECIST, adequate organ function, and those with advanced cancers associated with mesothelin expression are eligible for enrollment in the study.

The primary end points are to determine the MTD or recommended dose of CT-95 and to discover the incidence of treatment-emergent adverse events. Secondary end points include ORR, progression-free survival, overall survival, pharmacokinetics, and immunogenicity.

This trial is the second active study from Context Therapeutics Inc., the drug developer.¹ A trial evaluating CTIM-76, a Claudin 6 x CD3 T-cell engaging bispecific antibody in CLDN6-positive tumors, including ovarian, endometrial, and testicular cancers, dosed its first patient earlier this year.

References:

1. Context Therapeutics doses first patient in phase 1 clinical trial of CT-95. News release. Context Therapeutics, Inc. April 9, 2025. Accessed April 9, 2025. https://tinyurl.com/2s4j56u2

2. CT-95 in advanced cancers associated with mesothelin expression. ClinicalTrials.gov. Updated January 1, 2025. Accessed April 9, 2024. https://clinicaltrials.gov/study/NCT06756035?term=NCT06756035&rank=1