Lifileucel + Pembrolizumab for Melanoma

Recruiting at62 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Iovance Biotherapeutics, Inc.

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a Phase 3, multicenter, open-label, randomized, parallel group, treatment study to assess the efficacy and safety of lifileucel in combination with pembrolizumab compared with pembrolizumab alone in participants with untreated, unresectable or metastatic melanoma. Participants randomized to the pembrolizumab monotherapy arm who subsequently have a blinded independent central review- verified confirmed progressive disease (PD) will be offered lifileucel monotherapy in an optional crossover period.

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.

What data supports the effectiveness of the drug pembrolizumab for treating melanoma?

Pembrolizumab has shown high durable response rates in a large study of 411 patients with melanoma, with very little toxicity. It has been approved in the US for treating advanced melanoma, demonstrating robust antitumor activity and favorable safety. ^{1 2 3 4 5}

Is the combination of Lifileucel and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include immune-related issues like hypothyroidism (low thyroid function), colitis (inflammation of the colon), hepatitis (liver inflammation), and pneumonitis (lung inflammation). ^{2 3 5 6 7}

What makes the Lifileucel + Pembrolizumab treatment unique for melanoma?

This treatment combines Lifileucel, a type of cell therapy using tumor-infiltrating lymphocytes (TILs), with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against melanoma, offering a novel approach compared to traditional treatments. ^{1 2 3 5 7}

Research Team

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Lifileucel (CAR T-cell Therapy)
• Pembrolizumab (PD-1 Inhibitor)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Findings from Research

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]

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]

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]

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, 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) 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

3. United States 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). [2020]

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

Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]