Lifileucel + Pembrolizumab for Melanoma

Recruiting at 79 trial locations

Overseen By Iovance Biotherapeutics https://www.tilvance-301.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Iovance Biotherapeutics, Inc.

Disqualifiers: Uveal melanoma, Untreated brain metastases, Immunodeficiency, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

670 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining lifileucel and pembrolizumab compared to pembrolizumab alone for melanoma that cannot be surgically removed or has metastasized. Melanoma, a type of skin cancer, can become very serious if not treated effectively. Participants starting with pembrolizumab alone may switch to lifileucel if their disease progresses. Suitable candidates for this trial have advanced melanoma that has not been previously treated for metastatic disease and have at least one measurable tumor that can be removed for treatment purposes. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of promising new treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that combining lifileucel with pembrolizumab is generally safe for patients with advanced melanoma. Studies have reported some side effects, but they were mostly manageable. This combination has not caused any unexpected or serious safety issues.

The FDA has already approved pembrolizumab for treating melanoma, so its safety profile is well understood. Common side effects include fatigue, skin rash, and mild digestive problems, but these are usually mild.

Overall, both treatments have demonstrated a good safety record in past studies. While side effects can occur, they are usually not severe. For those considering joining this trial, evidence from previous research suggests that the treatment is generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lifileucel combined with Pembrolizumab for melanoma because Lifileucel is an innovative cell therapy that harnesses the patient's own immune cells, known as tumor-infiltrating lymphocytes (TILs), to target and destroy cancer cells. This approach is distinct from standard treatments like checkpoint inhibitors alone, as it directly amplifies the body's natural immune response against tumors. Moreover, the combination with Pembrolizumab, a well-established immunotherapy, could potentially enhance the effectiveness and durability of the treatment, offering new hope for patients with advanced melanoma.

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

Research shows that lifileucel combined with pembrolizumab may offer a promising treatment for advanced melanoma. In this trial, participants in Arm A will receive both lifileucel and pembrolizumab. Lifileucel has proven effective in patients with advanced melanoma who have not responded to other treatments. Studies have found that this combination can combat cancer when treatment options are limited. Participants in Arm B will receive pembrolizumab alone, a known treatment for melanoma that helps the immune system target and destroy cancer cells. The combination in Arm A aims to enhance its effectiveness, potentially improving outcomes for patients with difficult-to-treat melanoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Are You a Good Fit for This Trial?

This trial is for adults with untreated, unresectable or metastatic melanoma. They must have at least one lesion suitable for treatment creation, measurable disease, good organ function, and be willing to use effective birth control. Those over 70 may join after extra review. Exclusions include eye-origin melanoma, untreated brain metastases, more than one prior therapy line or any prior therapy for metastatic disease.

Inclusion Criteria

I have at least one tumor that can be surgically removed for treatment.

My organs are functioning well.

Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.

Exclusion Criteria

I have received treatment for cancer that has spread.

My tumor has a BRAF V600 mutation and I've only had immune therapy before surgery.

I have brain metastases that haven't been treated and are causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lifileucel plus pembrolizumab or pembrolizumab alone

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Optional Crossover Period

Participants in the pembrolizumab monotherapy arm with confirmed progressive disease may receive lifileucel monotherapy

What Are the Treatments Tested in This Trial?

Interventions

• Lifileucel
• Pembrolizumab

Trial Overview The study compares the effectiveness of a new combination treatment (Lifileucel plus Pembrolizumab) against Pembrolizumab alone in advanced melanoma patients. Participants are randomly assigned to either group and those on just Pembrolizumab can switch to Lifileucel if their disease progresses.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

Lifileucel plus Pembrolizumab

Group II: Arm B Active Control 1 Intervention

Pembrolizumab alone with Optional Crossover Period

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?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a real-world study of 532 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 21.8 months, indicating its effectiveness outside of clinical trials.

Patients with better performance status (ECOG 0-1), normal LDH levels, and no recent corticosteroid use had significantly improved overall survival, highlighting the importance of these factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. Liu, FX., Ou, W., Diede, SJ., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

Citations

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

Long-Term Efficacy and Safety of Lifileucel Tumor ... Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36600653/

Efficacy and safety of lifileucel, a one-time autologous tumor ... Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden.

3. iovance.com iovance.com/uploads/SMR-Thomas-IOV-COM-202-Cohort-1A-Encore-2807-publication.pdf

Efficacy and safety of lifileucel, an autologous tumor- ... overlap could be calculated. • A phase 3, randomized study to evaluate lifileucel + pembrolizumab in frontline advanced melanoma is currently.

4. 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 ... The goal of TILVANCE-301 is to understand more about the safety of lifileucel in combination with pembrolizumab compared to pembrolizumab alone ...

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

Review The Clinical TIL Experience in Melanoma In this review, we highlight key historical data for TIL therapy in melanoma as well as ongoing efforts to improve its efficacy and applicability.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9505

Efficacy and safety of lifileucel, an autologous tumor- ... This study evaluates lifileucel combined with anti-PD-1 therapy in front-line advanced melanoma. Methods: IOV-COM-202 (NCT03645928) Cohort 1A ...

7. iovance.com iovance.com/uploads/ASCO-2024-IOV-COM-202-Cohort-1A-05-31-24-2751-publication.pdf

ASCO-2024-IOV-COM-202-Cohort-1A- ... trial assessing lifileucel + pembrolizumab in frontline advanced melanoma. CR, complete response; DOR, duration of response; ICI, immune ...

8. tilvance-301.com tilvance-301.com/

TILVANCE-301 Study The TILVANCE-301 Study is evaluating the investigational agent, lifileucel, in combination with pembrolizumab, an ICI approved for the treatment of melanoma.