CT-95 for Cancer

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment CT-95 for cancer?

The research shows that similar treatments combining chemotherapy and radiotherapy have been effective in treating advanced head and neck cancers, with high rates of tumor response and organ preservation, although they come with significant side effects. ^{1 2 3 4 5}

How does the drug CT-95 for cancer differ from other treatments?

CT-95 may involve targeting the CD95 (Fas/APO-1) pathway, which is known for inducing cell death in cancer cells. This pathway can be activated by certain treatments, potentially making CT-95 unique by enhancing the body's ability to trigger cancer cell death through this mechanism. ^{6 7 8 9 10}

Research Team

Karen Smith, MD, PhD, MBA, LLM

Principal Investigator

Context Therapeutics Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant accelerated chemotherapy followed by hyperfractionated radiation therapy in patients with operable, locally advanced head and neck carcinoma. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous chemoradiotherapy in locally advanced cancer of the oral cavity and oropharynx. [2019]

3. Germany 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. [2021]

4. Ireland 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. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Role of p53 in regulating constitutive and X-radiation-inducible CD95 expression and function in carcinoma cells. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells. [2017]

8. England 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. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

CD95 gene deletion may reduce clonogenic growth and invasiveness of human glioblastoma cells in a CD95 ligand-independent manner. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Tumor therapeutics by design: targeting and activation of death receptors. [2017]