Cholangiocarcinoma Advanced, Cholangiocarcinoma Non-resectable, Colorectal Cancer, Epithelial Ovarian Cancer, Lung Adenocarcinoma Metastatic, Malignant Peritoneal Mesothelioma, Advanced, Malignant Pleural Mesothelioma, Advanced, Mesothelin-expressing Advanced Cancers, Mesothelin-Expressing Tumors, Mesothelin-positive Advanced Malignant Solid Tumors, Pancreatic Adenocarcinoma Advanced or Metastatic
Conditions
Keywords
Phase 1 Dose Escalation Study, CT-95, Advanced, recurrent cancers, Unresectable, metastatic cancers, Cancers associated with mesothelin expression
Brief summary
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.
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.
Interventions
DRUGCT-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.
Sponsors
Context Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTContext Clinical Development
STUDY_DIRECTORKaren Chagin, MD
Context Therapeutics Inc.
Outcome results
None listed