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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SynKIR-110 to determine its safety and effectiveness for individuals with certain advanced cancers, including ovarian cancer. SynKIR-110 uses modified immune cells (autologous T cells transduced with Mesothelin KIR-CAR) to target and attack cancer cells with a specific marker called mesothelin. The trial seeks participants with advanced ovarian cancer, primary peritoneal cancer, fallopian tube cancer, cholangiocarcinoma (a type of bile duct cancer), or epithelial mesothelioma who have not succeeded with other treatments. Participants should have a measurable tumor and maintain good general health despite their cancer. The goal is to discover if this one-time IV treatment can combat these hard-to-treat cancers. As a Phase 1 trial, this research aims to understand how SynKIR-110 works in people, offering participants the chance to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that SynKIR-110 is likely to be safe for humans?

Research has shown that SynKIR-110 is a new treatment using specially modified T cells to target certain cancer cells. It is designed to attack tumors with a protein called mesothelin, often found in ovarian cancer. Before human testing, SynKIR-110 showed promise in lab studies, which found that its cancer-fighting ability increased with higher doses.

Currently, SynKIR-110 is in the early stages of human testing, so researchers are just beginning to learn about its safety. As this is the first human trial, there is limited information on how well people tolerate the treatment or what side effects might occur. However, another study focused on the long-term safety of SynKIR-110 shows that researchers are committed to understanding its effects over time.

Prospective participants should know that safety is a top priority, and the team will closely monitor for any adverse effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Unlike the standard treatments for ovarian cancer, which often include chemotherapy, surgery, or targeted therapies, SynKIR-110 offers a novel approach by using autologous T cells transduced with Mesothelin KIR-CAR. This treatment is unique because it harnesses the patient's own immune cells, specifically modifying them to target and attack cancer cells expressing mesothelin, a protein commonly found on ovarian cancer cells. Researchers are excited about SynKIR-110 because it represents a personalized therapy that could potentially provide a more targeted and effective attack against cancer cells, with the promise of fewer side effects compared to traditional treatments. Additionally, its single-dose gravity drip IV administration makes it a straightforward option for patients.

What evidence suggests that SynKIR-110 might be an effective treatment for ovarian cancer?

Research has shown that SynKIR-110, the investigational treatment in this trial, could effectively target tumors with the protein mesothelin, often present in ovarian cancer. Lab studies demonstrated that SynKIR-110 kills cancer cells more effectively than a similar treatment, MSLN-41BBζ CAR T cells. SynKIR-110 uses specially modified T cells, a type of white blood cell, to locate and destroy cancer cells with mesothelin on their surface. Early tests suggest that higher doses improve the treatment's effectiveness. These findings offer hope that SynKIR-110 could become a strong option for treating certain advanced cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Laura Johnson, PhD

Principal Investigator

Verismo Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05568680

SynKIR-110 for Mesothelin Expressing Ovarian Cancer ... 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.

2. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A365

321 Preclinical potency assessment of SynKIR-110, a ... The preclinical study demonstrates that the anti-tumor efficacy of SynKIR-110 is dose dependent with greater potency compared to MSLN-41BBζ CAR T cells.

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/autologous-anti-mesothelin-kir-car-transduced-t-cells-synkir-110

autologous anti-mesothelin KIR-CAR-transduced T cells ... Upon administration, the autologous anti-MSLN KIR-CAR-transduced T cells SynKIR-110 specifically target and kill MSLN-expressing tumor cells. Mesothelin, a ...

4. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00160136

A Phase I Study of SynKIR-110, Autologous T cells ... A Phase I Study of SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR, in Subjects with Mesothelin-Expressing Advanced Ovarian Cancer, ...

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0680.html

A phase 1 study of SYNKIR-110, autologous t cells ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06377202

Long-Term Follow-Up Safety Study of Subjects Treated ... The primary objective of this study is to evaluate the long-term safety of SynKIR- 110 administered to adult subjects with solid tumors expressing mesothelin.