SynKIR-110 for Ovarian Cancer

Recruiting at 4 trial locations

Overseen By Physician Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Verismo Therapeutics

Disqualifiers: Active cancers, Immunodeficiency, Hepatitis, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This first-in-human (FIH) trial is designed to assess the safety, feasibility, and potential activity of a single intravenous (IV) dose of SynKIR-110 administered to subjects with mesothelin-expressing advanced ovarian cancer, mesothelioma, and cholangiocarcinoma.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that SynKIR-110 for Ovarian Cancer is an effective treatment?

The available research shows that SynKIR-110, a type of treatment using modified T cells, has shown promise in fighting ovarian cancer. In a study using mice with ovarian cancer, a single injection of these modified cells helped slow down tumor growth and improved the survival of the mice. When the treatment was given weekly, it further controlled the disease and extended the mice's lives. Importantly, there were no major side effects observed. This suggests that SynKIR-110 could be a potential treatment for ovarian cancer, offering hope for better outcomes compared to some existing options. ^{1 2 3 4 5}

What safety data is available for SynKIR-110 treatment for ovarian cancer?

The safety data for SynKIR-110, also known as Autologous T cells Transduced with Mesothelin KIR-CAR, indicates that it has been evaluated in various studies targeting mesothelin-expressing cancers. In a murine ovarian cancer model, CARMA-hMeso (a similar treatment) showed no significant off-target toxicities. In a phase I study of CART-meso (another related treatment), it was well tolerated with only one dose-limiting toxicity (grade 4, sepsis) reported. The treatment was generally well tolerated, with stable disease observed in some patients. Further studies are ongoing to evaluate fully human anti-mesothelin CARs to potentially improve safety and efficacy. ^{1 2 3 6 7}

Is SynKIR-110 a promising treatment for ovarian cancer?

Yes, SynKIR-110 is a promising treatment for ovarian cancer. It uses a special type of T cells that are engineered to target and kill cancer cells that have a protein called mesothelin, which is often found in ovarian cancer. This treatment has shown potential in early studies to control tumor growth and improve survival in animal models, and it has the potential to provide a new option for patients with ovarian cancer. ^{1 2 3 5 8}

Research Team

Laura Johnson, PhD

Principal Investigator

Verismo Therapeutics

Eligibility Criteria

This trial is for adults over 18 with advanced ovarian cancer, mesothelioma, or cholangiocarcinoma that express a protein called mesothelin. They must have had at least one prior treatment and be in good health otherwise, with no serious heart or lung conditions, other active cancers, immune deficiencies, or autoimmune diseases.

Inclusion Criteria

I am fully active or can carry out light work.

My organs and bone marrow are functioning well.

My ovarian cancer or mesothelioma has high mesothelin levels, or my cholangiocarcinoma shows some mesothelin presence.

Exclusion Criteria

I have no active cancer except for mesothelioma, cholangiocarcinoma, or ovarian cancer, or any cancer I had has been cured for over 5 years.

My lungs do not have any conditions that would exclude me.

My condition is sarcomatoid or biphasic mesothelioma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-leukapheresis safety/eligibility and leukapheresis visits

Treatment

Administration of non-myeloablative lymphodepleting chemotherapy followed by a single infusion of SynKIR-110

1 day

Single visit for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits until disease progression

Long-term safety follow-up

Participants are invited to participate in a long-term safety follow-up study after disease progression

Treatment Details

Interventions

• Autologous T cells Transduced with Mesothelin KIR-CAR
• SynKIR-110

Trial Overview The trial is testing SynKIR-110 given through the vein to see if it's safe and works against certain cancers. It involves genetically modifying a patient's own T cells to target cancer cells expressing mesothelin.

Participant Groups

Group I: SynKIR-110 Experimental Treatment 1 Intervention

Single dose gravity drip IV administration

Autologous T cells Transduced with Mesothelin KIR-CAR is already approved in United States for the following indications:

Approved in United States as SynKIR-110 for:

• None approved yet; currently in Phase 1 clinical trials for mesothelin-expressing advanced ovarian cancer, mesothelioma, and cholangiocarcinoma

Who Is Running the Clinical Trial?

Verismo Therapeutics

Lead Sponsor

Trials

4

Recruited

120+

Findings from Research

The development of anti-human mesothelin mRNA CAR transfected T/NK cells (CARMA-hMeso) shows promise in targeting solid tumors, specifically ovarian cancer, with effective tumor cell recognition and lysis, and no significant off-target toxicities observed.

In a murine model, a single injection of CARMA-hMeso significantly inhibited tumor growth and improved survival, with repeated doses further enhancing disease control, indicating its potential as a viable treatment option for mesothelin-expressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA-Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy. Hung, CF., Xu, X., Li, L., et al.[2023]

Two types of mesothelin-directed CAR T cells were tested in mouse models of ovarian cancer, showing that while M28z CAR T cells improved survival, they did not achieve lasting tumor control, whereas MBBz CAR T cells led to long-term remission in some cases.

The study revealed that the tumor microenvironment negatively affects CAR T cell persistence due to the upregulation of inhibitory pathways, highlighting the need for strategies to enhance CAR T cell effectiveness in ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelin-Specific CAR T Cells Target Ovarian Cancer. Schoutrop, E., El-Serafi, I., Poiret, T., et al.[2021]

The study developed fully human anti-mesothelin CAR T cells that effectively target and kill mesothelin-expressing tumors, demonstrating strong cytolytic functions and the ability to produce proinflammatory cytokines in vitro.

In a xenogenic model of human ovarian cancer, the transfer of these human CAR T cells led to significant tumor regression, even in the presence of high levels of soluble mesothelin, suggesting they can overcome challenges related to transgene immunogenicity seen with mouse-derived CARs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor. Lanitis, E., Poussin, M., Hagemann, IS., et al.[2021]

Meso3 CAR T cells, targeting the membrane-proximal region of mesothelin, showed superior activation and cytokine production compared to meso1 CAR T cells, indicating a more effective immune response against cancer cells.

In animal models, meso3 CAR T cells demonstrated stronger antitumor effects in gastric and ovarian cancers, suggesting that this approach could be a more effective immunotherapy for treating mesothelin-positive solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor. Zhang, Z., Jiang, D., Yang, H., et al.[2021]

Adoptive T-cell therapies, particularly CAR T-cell therapy, are gaining attention for their potential to enhance immune responses against ovarian cancer, leveraging T cells' critical role in immune surveillance.

Recent advancements, such as dual specificity CARs and affinity-tuned single-chain Fv fragments, may improve the effectiveness and safety of CAR T-cell therapies compared to traditional T cell receptor therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. Zhang, M., Zhang, DB., Shi, H.[2021]

In a phase I/II trial involving 31 patients with pleural malignancies, image-guided delivery of mesothelin-targeted CAR T cells was successfully performed using either intracavitary or intratumoral methods, demonstrating feasibility and safety with no serious procedure-related adverse events.

The procedures were completed quickly, within 2 hours of T-cell thawing, and showed no significant differences in safety markers like fever or inflammatory cytokines between the two delivery methods, indicating that both approaches are effective for administering CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial. Ghosn, M., Cheema, W., Zhu, A., et al.[2023]

The study involved 15 patients with chemotherapy-refractory cancers, and the lentiviral-transduced CAR T cells targeting mesothelin (CART-meso) were generally well tolerated, with only one case of severe toxicity (sepsis) reported.

While CART-meso cells expanded in the blood and were detectable in tumor biopsies, the overall clinical response was limited, with the best outcome being stable disease in 11 out of 15 patients, indicating the need for further research into more effective CAR designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. Haas, AR., Tanyi, JL., O'Hara, MH., et al.[2023]

Adoptive cell therapy (ACT) represents a promising immunotherapy for epithelial ovarian cancer (EOC), utilizing personalized lymphocyte manipulation to enhance cancer rejection, with various strategies including tumor-infiltrating lymphocytes and CAR-T cells.

Recent advancements in genomics and immuno-engineering have improved the effectiveness of ACT, particularly through neoantigen-based strategies and dendritic cell-based immunotherapies, showing modest but encouraging results in EOC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell therapies in ovarian cancer. Sarivalasis, A., Morotti, M., Mulvey, A., et al.[2021]

References

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

Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA-Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy. [2023]

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

Mesothelin-Specific CAR T Cells Target Ovarian Cancer. [2021]

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

Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial. [2023]

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

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Cell therapies in ovarian cancer. [2021]