Genetically-Engineered Immune Cells for Lung Cancer

(CheckCell-2 Trial)

Not yet recruiting at 1 trial location
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Intima Bioscience, Inc.
Must be taking: Anti-PD-1/PD-L1 immunotherapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for metastatic non-small cell lung cancer (NSCLC) using genetically-engineered immune cells. The treatment modifies Tumor Infiltrating Lymphocytes (TIL) to enhance their effectiveness against cancer cells by inactivating CISH, a gene that can limit immune response. The trial will assess the safety and effectiveness of this approach, with different trial groups based on specific cancer characteristics. Individuals with confirmed metastatic NSCLC who have started or are about to start certain cancer treatments may be eligible to participate. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use systemic steroids (except certain contraceptives) within 21 days before the investigational treatment and after. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Tumor Infiltrating Lymphocytes (TILs) can effectively treat certain cancers, such as non-small cell lung cancer (NSCLC). TILs, a type of immune cell, can attack cancer cells. Some studies have demonstrated their potential to provide lasting and meaningful benefits for patients.

This trial employs a special method called CRISPR to edit genes in these TILs. By turning off a specific gene called CISH, the TILs might work more effectively. In animal studies, disabling CISH in TILs has enhanced their ability to fight tumors.

While these studies are promising, it is important to note that this trial is in an early stage (Phase 1/2). This means the treatment is still being tested for safety and tolerance. Early-stage trials often focus on determining the right dose and checking for any side effects. So far, TIL therapy has generally been well-tolerated in other types of cancer. However, any new treatment may carry risks that are not yet fully understood.

Prospective participants should discuss all potential risks and benefits with their doctor before joining this trial.12345

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

Researchers are excited about CISH inactivated TILs for lung cancer because these treatments leverage a cutting-edge genetic engineering technique using CRISPR to modify tumor-infiltrating lymphocytes (TILs). Unlike traditional therapies like chemotherapy or radiation, which attack cancer cells and can harm healthy cells, this approach enhances the body's own immune cells to specifically target and destroy cancer cells. Another unique feature is the use of high-dose aldesleukin to boost immune response, with some treatment arms also including pembrolizumab to maintain the immune attack against cancer. This personalized and precise method of treatment has the potential to offer more effective and targeted outcomes than current standards of care.

What evidence suggests that this trial's treatments could be effective for Metastatic Non-small Cell Lung Cancer?

Research has shown that specially modified immune cells, called Tumor Infiltrating Lymphocytes (TIL), could help treat advanced Non-small Cell Lung Cancer (NSCLC). In animal studies, turning off a specific checkpoint in these immune cells significantly improved their ability to attack cancer. This trial will examine CISH inactivated TIL therapy, which has already demonstrated lasting and significant results in lung cancer patients, particularly those who have never smoked. The CRISPR technique, used to modify these cells, is known for its accuracy in enhancing immune cell function, potentially making these treatments more effective. Overall, this method offers hope for new possibilities for people with NSCLC.13567

Who Is on the Research Team?

EL

Emil Lou, MD, PhD

Principal Investigator

Division of Hematology, Oncology, and Transplantation, University of Minnesota

EM

Erminia Massarelli, MD, PhD, MS

Principal Investigator

Department of Medical Oncology & Therapeutics Research, City of Hope

Are You a Good Fit for This Trial?

Adults aged 18-70 with metastatic non-small cell lung cancer (NSCLC), either PD-L1 negative or positive, who are candidates for first-line anti-PD-1/anti-PD-L1 immunotherapy with chemo. They must have good organ function, agree to use contraception, and can stay near the treatment site for follow-ups. Exclusions include those with certain medical conditions, prior malignancies within 3 years, severe allergies to specific drugs, recent live vaccines, active infections or coagulation disorders.

Inclusion Criteria

I agree to stay near the treatment site until the 4-week follow-up.
Your blood test results from the past 3 months meet certain requirements.
Voluntary written consent prior to the performance of any research-related procedures
See 9 more

Exclusion Criteria

I have a health condition that may make it hard for me to handle strong cancer treatment.
I have had serious lung inflammation or currently have lung disease needing steroids.
I am currently dealing with an opportunistic infection.
See 13 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine, followed by CISH inactivated TIL and high-dose aldesleukin

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including maintenance pembrolizumab for some cohorts

3.5 years

Long-term follow-up

Participants are monitored for progression-free survival, duration of response, clinical benefit rate, tumor growth change, overall survival, and toxicity incidence

2-5 years

What Are the Treatments Tested in This Trial?

Interventions

  • CISH Inactivated TIL
Trial Overview The trial is testing genetically-engineered Tumor Infiltrating Lymphocytes (TIL) where CISH has been inactivated using CRISPR gene editing. This is combined with standard treatments like Pembrolizumab and chemotherapy to see if it's safe and effective against metastatic NSCLC.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: CISH CRISPR TIL plus pembrolizumab / Phase I ArmExperimental Treatment5 Interventions
Group II: CISH CRISPR TIL / Phase II Arm PD-L1 Positive CohortExperimental Treatment5 Interventions
Group III: CISH CRISPR TIL / Phase II Arm PD-L1 Negative CohortExperimental Treatment5 Interventions
Group IV: CISH CRISPR TIL / Phase I ArmExperimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Intima Bioscience, Inc.

Lead Sponsor

Trials
2
Recruited
90+

Published Research Related to This Trial

CAR-T cell therapies have shown significant clinical success in treating cancer by effectively targeting tumor-associated antigens, leading to complete and durable responses in many patients during early trials.
Despite their effectiveness, there are safety concerns regarding potential toxicities from engineered cells, prompting the exploration of strategies like integrating failsafe switches to enhance safety in cancer immunotherapy.
Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns.Resetca, D., Neschadim, A., Medin, JA.[2018]
CAR-T cell therapy has shown remarkable success in treating blood cancers, but its effectiveness against solid tumors is limited due to the immunosuppressive environment of these tumors.
There is a pressing need for the development of next-generation personalized CAR-T cells targeting solid tumors, focusing on improving their efficacy, survival, persistence, and safety, particularly in lung cancer.
CAR-T Cells for the Treatment of Lung Cancer.Chocarro, L., Arasanz, H., Fernández-Rubio, L., et al.[2022]
The TIL 3.0 method, which uses IL-2 combined with agonistic antibodies, significantly enhances the expansion of tumor-infiltrating lymphocytes (TIL) from non-small cell lung cancer (NSCLC) tumors, producing 5.3 times more TIL compared to the traditional TIL 1.0 method.
TIL 3.0 not only increases the quantity of CD8+ TIL but also maintains a diverse T-cell repertoire that closely resembles the original tumor's clonal hierarchy, suggesting a greater potential for effective adoptive cell transfer therapies in NSCLC.
Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes.Shah, P., Forget, MA., Frank, ML., et al.[2022]

Citations

Study Details | NCT05566223 | CISH Inactivated TILs in the ...A clinical trial to assess the safety and efficacy of genetically-engineered Tumor Infiltrating Lymphocytes (TIL) in which the intracellular immune checkpoint ...
Non-small Cell Lung Cancer, NSCLC, (NCT05566223)The inhibition of CISH in mouse anti-tumour lymphocytes results in a marked increase in the ability of these lymphocytes to mediate tumour ...
Tumor-Infiltrating Lymphocyte Therapy: A New FrontierThis trial indicated that TIL therapy could achieve durable and meaningful responses in NSCLC, including in the important subset of never-smoker lung cancer ...
TIL Therapy in Lung Cancer: Current Progress and PerspectivesUnveiling the promise of Tumor-Infiltrating Lymphocytes (TIL) therapy for lung cancer treatment. This review introduces why TIL therapy is ...
CRISPR/Cas9 technology for advancements in cancer ...CRISPR/Cas9 gene editing technology can accurately modify immune and tumour cells in tumours, and improve the efficacy of immunotherapy.
Tumor-Infiltrating Lymphocyte Therapy: A New FrontierThis trial indicated that TIL therapy could achieve durable and meaningful responses in NSCLC, including in the important subset of never-smoker lung cancer ...
Internal checkpoint regulates T cell neoantigen reactivity and ...These data indicate that loss of neoantigen reactivity after traditional TIL REP can be restored by CISH KO, resulting in a significant increase in TIL ...
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