Lifileucel + Chemo for Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Antineoplastics, Investigational agents

Disqualifiers: Pregnancy, Active infections, Organ allograft, 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: 28

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lifileucel, a type of cell therapy, for individuals with melanoma that cannot be surgically removed or has metastasized. The treatment uses special immune cells from the patient's own tumor to target the cancer. Suitable candidates have melanoma unresponsive to previous treatments, including specific drug therapies, and possess at least one tumor that can be removed for this process. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 28 days from prior anticancer therapies before starting the study treatment. This includes targeted therapy, chemotherapy, and immunotherapy. You should discuss your specific medications with the trial team to understand how this applies to you.

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

Research shows that lifileucel is generally well-tolerated by patients with advanced melanoma. In earlier studies, most side effects appeared soon after treatment and related to the preparatory steps before receiving lifileucel. The most common serious side effects included low platelet count (thrombocytopenia), low red blood cell count (anemia), and fever with low white blood cells (febrile neutropenia), affecting over 30% of patients. However, new or late side effects were usually not linked to lifileucel itself.

Patients treated with lifileucel lived for a median of about 14 months, and nearly 20% survived beyond five years. This suggests that lifileucel has a manageable safety profile and could be a promising option for those with melanoma that cannot be surgically removed or has metastasized. ^{1 2 3 4 5}

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

Researchers are excited about lifileucel for treating melanoma because it uses a novel approach called autologous Tumor Infiltrating Lymphocytes (TIL) cell therapy. Unlike standard treatments like checkpoint inhibitors and targeted therapies, lifileucel involves resecting a tumor sample from the patient and using it to manufacture a personalized cell therapy. This means the treatment is tailored to each individual's cancer, potentially improving effectiveness. Additionally, lifileucel is combined with interleukin-2 to boost the immune response, offering a new mechanism that could enhance the body's ability to fight melanoma.

What evidence suggests that Lifileucel combined with chemotherapy could be effective for melanoma?

Research has shown that lifileucel, which participants in this trial will receive, may help treat advanced melanoma. Lifileucel uses a patient's own immune cells to combat the cancer. Studies found that about one-third of patients (31.4% to 36%) experienced tumor shrinkage. In some cases, patients saw long-lasting benefits, with tumors shrinking or even disappearing. Additionally, 79.3% of patients had some reduction in tumor size. These findings suggest that lifileucel could be a promising option for patients with hard-to-treat melanoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Muhammad Umair Mushtaq

Principal Investigator

University of Kansas

Are You a Good Fit for This Trial?

This trial is for adults with unresectable or metastatic melanoma who have progressed after 1-3 systemic therapies, including a PD-1 inhibitor. If they have a BRAF V600 mutation, they must have had BRAF/MEK inhibitors. They need at least one measurable lesion and good organ function. Exclusions include primary immunodeficiency, severe lung function impairment, untreated brain metastases, certain heart conditions, pregnancy/breastfeeding, and recent other cancers.

Inclusion Criteria

My immune therapy-related hormone issues have been stable for 6 weeks and are controlled without steroids.

Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 12 months following the last dose of IL-2 or until the first dose of the next anti-cancer therapy, whichever occurs first

My cancer has grown in an area previously treated with radiation, but it's been over 3 months since that treatment.

Exclusion Criteria

Your lung function test shows that you have difficulty breathing out air quickly.

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

I am not using, nor plan to use other cancer treatments during this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tumor Resection and Manufacturing

Patients undergo tumor resection surgery and lifileucel is manufactured

4 weeks

Lymphodepletion and Treatment

Patients receive cyclophosphamide and fludarabine for lymphodepletion, followed by lifileucel infusion and up to 6 doses of interleukin-2

1 week

In-patient hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at day 28, 42, 84, 126, 180, 365, month 18, and month 24

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Interleukin-2
• Lifileucel

Trial Overview The trial tests Lifileucel (T cells from the patient's tumor) combined with reduced doses of Fludarabine and Cyclophosphamide for lymphodepletion plus Interleukin-2 in patients with advanced melanoma. It aims to see if this approach helps the immune system attack the cancer more effectively.

How Is the Trial Designed?

Group I: Treatment (Lifileucel) Experimental Treatment 9 Interventions

Lifileucel (LN-144) is an autologous Tumor Infiltrating Lymphocytes (TIL) cell therapy. A tumor sample is resected from each patient for lifileucel manufacturing. Patients then receive the lifileucel regimen which consists of a reduced dose non-myeloablative lymphodepletion, lifileucel infusion followed by interleukin-2.

Lifileucel is already approved in United States for the following indications:

Approved in United States as Lifileucel for:

• Unresectable or metastatic melanoma in adults who have previously been treated with a PD-1 inhibitor and, if BRAF-positive, a BRAF inhibitor with or without a MEK inhibitor

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

A systematic review and meta-analysis of 6 randomized trials involving 912 patients found that adding tamoxifen to chemotherapy regimens did not significantly improve the overall response rate or complete response rate in treating metastatic malignant melanoma.

The evidence suggests that tamoxifen does not enhance survival rates when used in combination with other systemic chemotherapy, indicating it may not be beneficial for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tamoxifen in the treatment of malignant melanoma. Lens, MB., Reiman, T., Husain, AF.[2018]

In a study involving 17 patients with advanced malignant melanoma, tamoxifen at a daily dose of 100 mg/m2 was found to be ineffective, as none of the patients experienced objective regression of their disease.

Most patients (71%) showed progressive disease after initial reassessment, and 24% experienced moderate to severe nausea, indicating that tamoxifen may not be a suitable treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of high-dose tamoxifen (NSC-180973) in patients with disseminated malignant melanoma. Creagan, ET., Ingle, JN., Ahmann, DL., et al.[2019]

In a Phase II study involving 46 patients with metastatic breast carcinoma, the TEMP regimen (tamoxifen, etoposide, mitoxantrone, and cisplatin) showed a 41% overall objective response rate, indicating its potential effectiveness in treating this patient population.

The TEMP regimen was particularly effective in patients who had previously received doxorubicin, achieving a 56% response rate among those treated in the adjuvant setting, suggesting a possible synergistic effect of tamoxifen when combined with other chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of tamoxifen, etoposide, mitoxantrone, and cisplatin in patients with metastatic breast carcinoma. Conzen, SD., Kaufman, PA., Arvizu, C., et al.[2019]

In a Phase I study involving three patients with advanced malignant melanoma, the proposed combination of chemotherapy and immunotherapy was found to be unfeasible due to significant side effects and difficulties in maintaining the planned treatment intensity.

Despite the challenges, the study suggests that combined chemo-immunotherapy could be a promising approach for treating metastatic melanoma, prompting modifications to the treatment schedule for better feasibility and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of repetitive courses of high-dose continuous intravenous infusion interleukin-2 and subcutaneous alpha-interferon with polychemotherapy in advanced malignant melanoma. Foppoli, M., Citterio, G., Polastri, D., et al.[2022]

Advanced cutaneous melanoma treatments have low response rates, with single-agent cytotoxic drugs yielding less than 20% effectiveness, while combination chemotherapy regimens show slightly better results of 20% to 40%.

Cisplatin-based combinations with interferon-alfa and interleukin-2 can achieve response rates of 50% to 60%, but these treatments come with severe toxicity and their long-term survival benefits are still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatments for advanced cutaneous melanoma. Anderson, CM., Buzaid, AC., Legha, SS.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40454684/

Long-term Efficacy and Safety of Lifileucel Tumor ... Overall, 79.3% of patients had tumor burden reduction; 16 had deepened responses with 4 converting from PR to CR > 1 year after lifileucel ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00765

Long-Term Efficacy and Safety of Lifileucel Tumor ... In the registrational C-144-01 study, patients who received lifileucel had an objective response rate (ORR) of 31.4%. ... We report 5-year ...

3. curemelanoma.org curemelanoma.org/blog/the-tilvance-301-trial-expanding-a-patients-own-tumor-fighting-cells-to-generate-a-long-term-response-in-advanced-melanoma

The TILVANCE-301 Trial: Expanding a Patient's Own ... Results presented in 2024 showed that more than two-thirds of patients responded to treatment and saw their tumors shrink or disappear. In many ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S266663672400784X

Review The Clinical TIL Experience in Melanoma The primary efficacy endpoints of complete response (CR) rate (24% vs. 24%) and median overall survival (38.2 vs. 36.6 months; hazard ratio [HR], 1.11; 95% ...

5. jitc.bmj.com jitc.bmj.com/content/10/12/e005755

Efficacy and safety of lifileucel, a one-time autologous ... Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% ...

6. iovance.com iovance.com/uploads/ASCO_2025_C-144-01_5_Year_Analysis-3086-publication.pdf

Lifileucel in patients with advanced melanoma: 5-year ... The incidence of adverse events (AEs) declined rapidly within 2 weeks after lifileucel infusion; new or late-onset AEs were not related to lifileucel. 2.