TIL Therapy for Cervical Cancer

No longer recruiting at 44 trial locations

Overseen By Iovance Biotherapeutics Clinical Inquiries

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Iovance Biotherapeutics, Inc.

Must not be taking: Steroids, Immunotherapy

Disqualifiers: Organ allograft, Brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for cervical cancer that has returned or spread after initial treatment. It tests a method where a patient's own immune cells, known as tumor infiltrating lymphocytes (TILs), are collected, multiplied, and reintroduced into the body to combat the cancer, sometimes with the drug pembrolizumab. The trial includes different groups, such as those who have tried similar treatments before and those combining therapies. This trial may suit individuals with cervical cancer that cannot be removed by surgery or radiation and who have already tried some chemotherapy options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that any prior therapy directed at the tumor, including chemotherapy, biologic/targeted agents, and immunologic agents, must be stopped at least 28 days before tumor resection. If you are on these types of medications, you will need to stop them before participating.

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

Research has shown that LN-145, whether used alone or with pembrolizumab, is generally safe. In a study involving patients previously treated for cervical cancer, LN-145 achieved a 44% overall response rate, indicating nearly half of the patients experienced positive results, and it was deemed safe. The benefits of the treatment persisted over time.

When combined with pembrolizumab, a treatment that aids the immune system in fighting cancer, LN-145 also demonstrated safety. No unexpected safety issues arose with this combination.

As this treatment undergoes testing in Phase 2 trials, researchers continue to gather information about its safety. However, evidence so far suggests that LN-145 and its combinations are well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cervical cancer, which often include surgery, chemotherapy, and radiation, LN-145 offers a unique approach by harnessing the body's own immune system. LN-145 is a type of tumor-infiltrating lymphocyte (TIL) therapy, which involves extracting and multiplying a patient's own immune cells that are capable of fighting cancer, then reintroducing them back into the patient. This personalized treatment is promising because it directly targets cancer cells with potentially fewer side effects than traditional therapies. Researchers are excited about LN-145 because it could provide a new option for patients who have already undergone other treatments, especially those who have been treated with checkpoint inhibitors like PD-1 or PD-L1.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

Research shows that LN-145, a treatment using a patient's own immune cells, holds promise for cervical cancer. In earlier studies, LN-145 led to a 44% overall response rate, with nearly half of the patients experiencing a significant reduction in tumor size. It proved both effective and safe for patients who did not respond to other treatments. In this trial, some participants will receive LN-145 monotherapy, while others will receive a combination of LN-145 and pembrolizumab, a drug that helps the immune system target and attack cancer cells. These findings suggest that LN-145 could be a helpful option for those with advanced cervical cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Iovance Medical Monitor

Principal Investigator

Iovance Biotherapeutics, Inc.

Are You a Good Fit for This Trial?

Adults over 18 with recurrent, metastatic, or persistent cervical cancer not treatable by surgery/radiation. Must have measurable lesions and be in good physical condition (ECOG 0-1). Previous systemic therapy is required; however, no more than three lines of chemotherapy for Cohorts 1 and 2. Participants must have adequate organ function, no active infections or HIV, and agree to contraception.

Inclusion Criteria

I have received bevacizumab and chemotherapy together before.

I have a tumor that can be surgically removed and is at least 1.5 cm wide.

At least one measurable target lesion, as defined by RECIST v1.1.

Exclusion Criteria

I am receiving a specific chemotherapy regimen before my transplant.

You have a condition that weakens your immune system, like severe combined immunodeficiency (SCID) or acquired immunodeficiency syndrome (AIDS).

My heart's pumping ability is below normal, or I have moderate to severe heart problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a non-myeloablative lymphodepleting preparative regimen

1 week

Treatment

Participants are infused with autologous TIL (LN-145) followed by IL-2 administration

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• LN-145
• Pembrolizumab

Trial Overview The trial studies LN-145 alone or combined with pembrolizumab in treating cervical carcinoma. It's a prospective study where patients receive TIL infusion after lymphodepletion. The goal is to evaluate the effectiveness of this adoptive cell therapy for those who've had previous treatments but still show disease progression.

How Is the Trial Designed?

Group I: Cohort 5 Retreatment Cohort Experimental Treatment 1 Intervention

Patients who have been previously treated with LN-145 may be given a second treatment with TIL.

Group II: Cohort 4 - Non-enrolling Cohort Experimental Treatment 1 Intervention

Cohort includes patient population not meeting inclusion criteria in cohort 1 and 2. Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group III: Cohort 3 - Combination Arm (TIL + Pembrolizumab) - US Only Experimental Treatment 1 Intervention

Patients will be administered with pembrolizumab, followed by NMA lymphodepletion, then infused with their autologous TIL (LN-145) followed by pembrolizumab every 3 or 6 weeks post IL-2 administration up to 24 months.

Group IV: Cohort 2 LN-145 monotherapy Experimental Treatment 1 Intervention

Patients previously treated with an antiprogrammed cell death protein-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) checkpoint inhibitor: Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

Group V: Cohort 1 LN-145 monotherapy Experimental Treatment 1 Intervention

Post-NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

LN-145 is already approved in United States for the following indications:

Approved in United States as LN-145 for:

• Cervical Cancer
• Metastatic Melanoma
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Non-Small Cell Lung Cancer (NSCLC)

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

A new method for isolating tumor-infiltrating lymphocytes (TIL) that express specific dysfunction markers (CD39, PD-1, and TIGIT) has been developed, allowing for efficient identification of neoantigen-reactive T-cell receptors (TCRs) from resected tumors, which is crucial for creating targeted cancer therapies.

Despite the initial success in isolating TIL with potential neoantigen reactivity, most expanded TIL populations showed functional impairment, indicating that while the isolation method is effective, the in vitro expansion process may hinder the TIL's ability to recognize and attack tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests. Chatani, PD., Lowery, FJ., Parikh, NB., et al.[2023]

In a Phase 2 trial involving 153 patients with advanced melanoma who had previously progressed on immune checkpoint inhibitors, lifileucel showed an objective response rate (ORR) of 31.4%, indicating its potential effectiveness in this challenging patient population.

The treatment demonstrated durable responses, with 41.7% of patients maintaining their response for at least 18 months, and a favorable safety profile, although common severe side effects included thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. Chesney, J., Lewis, KD., Kluger, H., et al.[2023]

A study analyzing tumor-infiltrating lymphocytes (TILs) from 11 breast cancer biopsies revealed that CD4+ TILs have distinct T cell receptor (TCR) characteristics compared to CD8+ TILs, including larger sequences and a higher usage of positively charged residues.

The CD4+ TILs exhibited a more restricted TCR repertoire with greater similarity among sequences, suggesting a potential tumor-driven adaptation that may enhance their ability to recognize and respond to cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response. Aran, A., Lázaro, G., Marco, V., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03108495

NCT03108495 | Study of LN-145, Autologous Tumor ... After reviewing available safety and efficacy data to date, Iovance concluded the study reached the required number of events for evaluation of study endpoints.

2. iovance.com iovance.com/uploads/Iovance_SITC-2021_Phase-2-Efficacy-and-Safety-of-Autologous-Tumor-Infiltrating-Lymphocyte.pdf

LN-145) monotherapy in patients with advanced, immune ch Phase 2 Efficacy and Safety of Autologous Tumor-Infiltrating. Lymphocyte (TIL) Cell Therapy in Combination with. Pembrolizumab in Immune Checkpoint Inhibitor- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.2538

Safety and efficacy of adoptive cell transfer using ... LN-145 results in 44% ORR in previously treated cervical cancer patients with acceptable safety and efficacy profile.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11294887/

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte ... In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell ...

5. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A523

492 Phase 2 efficacy and safety of autologous tumor ... We explored a combination of TIL and pembrolizumab in patients with ICI-naïve melanoma, head and neck squamous cell carcinoma (HNSCC), and cervical cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03108495

NCT03108495 | Study of LN-145, Autologous Tumor ... After reviewing available safety and efficacy data to date, Iovance concluded the study reached the required number of events for evaluation of study endpoints.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9748991/

Efficacy and safety of lifileucel, a one-time autologous tumor ... Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited ...

8. jitc.bmj.com jitc.bmj.com/content/jitc/9/Suppl_2/A523.full.pdf

492 Phase 2 efficacy and safety of autologous tumor- ... PHASE 2 EFFICACY AND SAFETY OF AUTOLOGOUS. TUMOR-INFILTRATING LYMPHOCYTE (TIL) CELL. THERAPY IN COMBINATION WITH PEMBROLIZUMAB IN. IMMUNE CHECKPOINT INHIBITOR ...