CT-95 for Cancer

Recruiting at 6 trial locations

Overseen By Curtis Reinard

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Context Therapeutics Inc.

Disqualifiers: Active infection, CAR-T therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CT-95, a drug specifically designed to target and attack advanced solid tumors that express the protein Mesothelin. The primary goal is to determine the safety and efficacy of CT-95 against these cancers. The trial includes different groups receiving varying doses to identify the optimal treatment amount. Suitable candidates for this trial have advanced cancers with Mesothelin and are in good general health, without active infections. As a Phase 1 trial, this research aims to understand how CT-95 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the CT-95 trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that CT-95 is likely to be safe for humans?

Research has shown that CT-95 has been safe in ongoing studies. Importantly, no reports of severe immune reactions or harmful side effects have emerged that would limit the treatment dosage. This suggests that CT-95 is well-tolerated so far. However, as this is an early-phase trial, researchers continue to closely monitor the treatment to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often include chemotherapy, radiation, and surgery, CT-95 is unique because it introduces a new mechanism of action. CT-95 targets cancer by selectively inhibiting a specific protein critical for tumor growth, potentially reducing harm to healthy cells. Researchers are excited about CT-95 because it offers the promise of fewer side effects and improved effectiveness, especially for patients who have not responded well to existing therapies. Additionally, the weekly dosing schedule in multiple dose cohorts allows for tailored treatment, making it a promising option in personalized cancer care.

What evidence suggests that CT-95 might be an effective treatment for cancer?

Research has shown that CT-95, the investigational treatment in this trial, targets mesothelin, a protein often present in certain cancer cells. Early lab studies demonstrated that CT-95 effectively activates T cells, a type of immune cell, to attack these cancer cells. Initial results suggest that CT-95 could be promising for treating cancers with mesothelin, such as some pancreatic tumors. Importantly, ongoing studies have shown that CT-95 maintains a good safety record, with no severe side effects reported so far. These findings support further research into its potential effectiveness against advanced solid tumors. ^{1 3 5 6 7}

Who Is on the Research Team?

Karen Chagin, MD

Principal Investigator

Context Therapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors that show Mesothelin expression, including various cancers like mesothelioma, ovarian, lung, pancreatic, and bile duct cancer. Specific eligibility criteria are not provided.

Inclusion Criteria

Subjects with evaluable disease per RECIST 1.1 or mRECIST

My organs are working well.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have previously received MSLN-targeted therapy.

I do not have any severe infections or health issues that would stop me from joining the study.

Concurrent participation in another investigational clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CT-95 weekly for each 28-day cycle until disease progression, unacceptable toxicity, or decision to discontinue

6 months

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants' overall survival is monitored

Up to 2 years post-first dose

What Are the Treatments Tested in This Trial?

Interventions

• CT-95

Trial Overview

The study is testing CT-95, a new type of antibody designed to target cancer cells expressing Mesothelin. It's an early-phase trial to see if it's safe and works well at different doses in patients with certain types of advanced cancers.

How Is the Trial Designed?

Group I: CT-95 Experimental Treatment 1 Intervention

Each dose cohort will have weekly dosing. Anticipate approximately 8 dose cohorts.

Who Is Running the Clinical Trial?

Context Therapeutics Inc.

Lead Sponsor

Trials

7

Recruited

260+

Published Research Related to This Trial

The study found that the CD95 pathway plays a crucial role in the apoptosis (cell death) of medulloblastoma and glioblastoma cells induced by chemotherapy and gamma-irradiation, highlighting a potential target for enhancing treatment efficacy.

Blocking the CD95 receptor significantly reduced apoptosis, indicating that therapies targeting this pathway could improve the effectiveness of existing treatments for childhood brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells. Fulda, S., Scaffidi, C., Pietsch, T., et al.[2017]

Wild-type p53 plays a crucial role in regulating the expression of the CD95 death receptor in carcinoma cells, as shown by reduced CD95 levels and apoptotic responses in p53-inactivated cell lines (HCT116 and MCF-7).

The study found that while ionizing radiation can induce CD95 expression, the resulting increase in cell death through CD95 ligation varies by cell type, indicating that the effectiveness of this mechanism may depend on the specific characteristics of the cancer cells involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of p53 in regulating constitutive and X-radiation-inducible CD95 expression and function in carcinoma cells. Sheard, MA., Uldrijan, S., Vojtesek, B.[2017]

In glioma-initiating cells (GIC), CD95 is expressed and can promote tumor growth independently of its ligand CD95L, suggesting a complex role in cancer biology.

Genetic deletion of CD95 did not improve survival in mice with GIC, indicating that while CD95 may have tumor-promoting effects, it is not essential for the growth of these tumors, complicating potential therapeutic strategies targeting CD95.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD95 gene deletion may reduce clonogenic growth and invasiveness of human glioblastoma cells in a CD95 ligand-independent manner. Quijano-Rubio, C., Silginer, M., Weller, M.[2022]

In a phase II trial involving 68 patients with advanced head and neck cancer, an accelerated chemotherapy regimen followed by hyperfractionated radiation therapy resulted in a 66% overall survival rate and a 76% disease-free survival rate at a median follow-up of 32 months.

The treatment achieved a high organ preservation rate of 73%, but also led to significant toxicity, with 75% of patients experiencing severe mucositis and an 18% incidence of chemotherapy-related cardiotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant accelerated chemotherapy followed by hyperfractionated radiation therapy in patients with operable, locally advanced head and neck carcinoma. Franchin, G., Vaccher, E., Gobitti, C., et al.[2013]

In a study of 324 patients with head and neck cancer, neoadjuvant chemotherapy with carboplatin and 5-fluorouracil (CT+LRT) led to a 29% reduction in the need for mutilating surgery compared to locoregional treatment alone (LRT), with a tumor objective response rate of 63%.

Despite the improved surgical outcomes, there was no significant difference in overall survival or disease-free survival rates between the CT+LRT group (56% and 33%, respectively) and the LRT group (46% and 30%, respectively), indicating that while chemotherapy may reduce surgery severity, it does not necessarily improve long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer. Depondt, J., Gehanno, P., Martin, M., et al.[2018]

In a phase II study involving 40 patients with unresectable head and neck tumors, combined chemoradiotherapy (CT/RT) resulted in a high clinical response rate of 90%, with 37% achieving a complete clinical response.

Despite significant toxicity, including severe mucositis in 55% of patients and a median weight loss of 7%, the treatment was manageable, leading to a pathologic complete response rate of 35% and a median survival of 23 months, with 47% of patients remaining disease-free after 21 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous chemoradiotherapy in locally advanced cancer of the oral cavity and oropharynx. del Campo, JM., Felip, E., Giralt, J., et al.[2019]

In a study of 128 patients with stage II/III colon carcinoma, loss of CD95 expression in tumor cells was linked to a worse prognosis, indicating it may serve as an independent prognostic factor.

Tumor-infiltrating lymphocytes (TIL) were the primary source of CD95L, and a higher presence of CD95L+TIL correlated with better disease-free survival in early-stage (UICC stage II) colon cancer, suggesting they may help control tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease. Sträter, J., Hinz, U., Hasel, C., et al.[2018]

In a study of 115 patients with locally advanced operable head and neck cancer, an intensive chemotherapy regimen followed by unconventional radiotherapy resulted in a high clinical complete remission rate of 97.2% for the primary site and 67.5% for neck nodes.

The treatment achieved a 5-year overall survival rate of 55% and a cause-specific survival rate of 73%, while maintaining a high organ preservation rate of 73.5%, despite some reported cardiotoxicity and severe mucositis in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ preservation in locally advanced head and neck cancer of the larynx using induction chemotherapy followed by improved radiation schemes. Franchin, G., Vaccher, E., Politi, D., et al.[2021]

In a phase II study involving 40 patients with stage III non-small-cell lung cancer, combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) resulted in minimal acute radiation toxicity and no significant late toxicities.

The treatment achieved a response rate of 65%, with median overall survival of 15.7 months, indicating that this approach is both safe and potentially effective, warranting further comparison with synchronous chemoradiation for toxicity and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of induction chemotherapy followed by continuous hyperfractionated accelerated radiotherapy in locally advanced non-small-cell lung cancer. Jenkins, P., Anderson, S., Wronski, S., et al.[2018]

Death receptor ligands like TNF, CD95L, and TRAIL have strong potential as cancer treatments due to their ability to induce cell death, but challenges remain in their delivery and specificity.

Recent advancements in gene therapy and the development of new cytokine variants, including fusion proteins, show promise in enhancing the targeted anti-tumor effects of these ligands while minimizing side effects, potentially improving their therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor therapeutics by design: targeting and activation of death receptors. Wajant, H., Gerspach, J., Pfizenmaier, K.[2017]

Citations

1.

targetedonc.com

targetedonc.com/view/ct-95-phase-1-trial-enrolls-and-doses-first-patient-with-msln-advanced-cancer

CT-95 Phase 1 Trial Enrolls and Doses First Patient With ...

A phase 1 open-label trial is underway, evaluating the safety and efficacy of CT-95 in patients with mesothelin-expressing advanced solid tumors.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06756035

NCT06756035 | CT-95 in Advanced Cancers Associated ...

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 ...

3.

ir.contexttherapeutics.com

ir.contexttherapeutics.com/node/8451/pdf

Preclinical and Translational Data for CT-95, a Mesothelin ...

“We believe these preclinical and translational data support the clinical strategy to target mesothelin expressing cancers, including pancreatic ...

4.

curetoday.com

curetoday.com/view/first-patient-dosed-in-trial-of-ct-95-in-mesothelin-expressing-tumors

First Patient Dosed in Trial of CT-95 in Mesothelin ...

The first patient has been dosed in a phase 1 clinical trial of CT-95 among patients with mesothelin-expressing solid tumors.

5.

quiverquant.com

quiverquant.com/news/Context+Therapeutics+Inc.+Presents+Data+on+CT-95+and+CT-202+Bispecific+Antibodies+at+SITC+2025+Annual+Meeting

Context Therapeutics Inc. Presents Data on CT-95 and CT ...

CT-95 has shown a favorable safety profile in an ongoing Phase 1 trial, with no severe cytokine release syndrome or dose limiting toxicity ...

6.

biospace.com

biospace.com/press-releases/context-therapeutics-highlights-ct-95-and-ct-202-programs-at-2025-sitc-annual-meeting

Context Therapeutics Highlights CT-95 and CT-202 ...

Based on preclinical data, CT-95 is projected to achieve target dose exposure starting at Cohort 4.

7.

finance.yahoo.com

finance.yahoo.com/news/context-therapeutics-highlights-ct-95-123000941.html

Context Therapeutics Highlights CT-95 and CT-202 ...

Based on preclinical data, CT-95 is projected to achieve target dose exposure starting at Cohort 4.