TIL Therapy for Cervical Cancer

Recruiting at 42 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

189 Participants Needed

Trial Summary

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.

What data supports the effectiveness of this treatment for cervical cancer?

Research shows that tumor-infiltrating lymphocyte (TIL) therapy, which involves using a patient's own immune cells to fight cancer, has shown promising results in treating cervical cancer. In one case, a patient with recurrent cervical cancer achieved complete response after receiving TIL therapy, indicating its potential effectiveness. ^{1 2 3 4 5}

Is TIL therapy safe for humans?

TIL therapy has been generally safe in humans, with some studies reporting manageable side effects like fever and low blood cell counts. In cervical cancer, modified treatment strategies have shown negligible adverse reactions, and in other cancers, severe side effects were rare. ^{5 6 7 8 9}

How is TIL therapy for cervical cancer different from other treatments?

TIL therapy for cervical cancer is unique because it uses a patient's own immune cells, specifically tumor-infiltrating lymphocytes, to target and kill cancer cells, offering a personalized treatment approach. Unlike traditional therapies, it involves a modified lymphodepleting regimen that reduces severe side effects, and it has shown promising results in achieving complete response in some patients. ^{1 2 4 5 10}

What is the purpose of this trial?

Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma

Research Team

Iovance Medical Monitor

Principal Investigator

Iovance Biotherapeutics, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy. [2021]

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

Prognostic and therapeutic TILs of cervical cancer-Current advances and future perspectives. [2021]

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

Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients? [2020]

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

Isolation and characterization of tumor-infiltrating lymphocytes from cervical carcinoma. [2020]

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

Eradicating tumor in a recurrent cervical cancer patient with autologous tumor-infiltrating lymphocytes and a modified lymphodepleting regimen. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests. [2023]

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

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer. [2022]

8. England 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. [2023]

9. China pubmed.ncbi.nlm.nih.gov

[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma]. [2022]

10. Switzerland 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. [2023]