Evaluating Lifileucel and Pembrolizumab in Advanced Melanoma

Metastatic melanoma dermoscopy

Image credit: DermNet

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held earlier this month, Iovance Biotherapeutics presented updated data and translational data on lifileucel in combination with pembrolizumab for the treatment of frontline advanced melanoma. Positive results from cohort 1A of the IOV-COM-202 trial were highlighted in an oral presentation as ASCO 2024. Notably, “Unprecedented response rates, as well as deep and durable responses, were observed in patients with frontline advanced melanoma who were naïve to immune checkpoint inhibitor ICI therapy. These results strongly support the ongoing phase 3 TILVANCE-301 clinical trial.”¹

Dermatology Times spoke with Peter Prieto, MD, MPH, the senior vice president of medical affairs at Iovance Biotherapeutics, to learn more about the IOV-COM-202 trial evaluating lifileucel alone or in combination with immune checkpoint inhibitors in patients with advanced solid tumors such as melanoma.

Q&A With Peter Prieto, MD, MPH

Dermatology Times: Can you please provide a brief overview of the IOV-COM-202 study and its design? 

Prieto: IOV-COM-202 is a phase 2 study assessing TIL therapy (lifileucel, LN-145, LN-144, and LN-145-S1) alone or in combination with immune checkpoint inhibitors (ICI) in patients with advanced solid tumors, which include those with melanoma, non-small cell lung cancer, and head and neck cancer. Cohort 1A, which was presented at ASCO 2024, evaluated lifileucel and pembrolizumab in patients with ICI-naïve unresectable or metastatic melanoma. If BRAF-positive, patients may have received a BRAF/MEK inhibitor. This analysis at ASCO included 23 patients

Dermatology Times: How do the response rates observed in this study compare with historical response rates for pembrolizumab monotherapy in similar patient populations? 

Prieto: While we cannot make any direct comparisons to other trials at this time, the response rates seen in Cohort 1A of the trial are unprecedented in the field of solid tumor immunotherapy. The compelling response rates, including a 30.4% complete response rate, and depth and durability of responses for lifileucel in combination with pembrolizumab strongly support our strategy in frontline advanced melanoma. TILVANCE-301, a phase 3 trial, is underway in the same patient population to support accelerated and full U.S. approvals of lifileucel in combination with pembrolizumab in frontline advanced melanoma.

Dermatology Times: What key data points from the study are most important for dermatology clinicians to know right now? 

Prieto: In addition to the unprecedented response rates seen from this study – showing the objective response rate (ORR) was 65.2% and complete response rate (CRR) was 30.4% the overall data strongly support the potential of lifileucel to benefit patients with advanced melanoma in the frontline setting. The data are welcome news for clinicians, as it underscores the potential of this one-time, personalized therapy to transform the treatment paradigm for those with advanced melanoma, a population with significant unmet treatment needs. Along with clinicians, I look forward to results from the TILVANCE-301 study to learn more about how this combination regimen may benefit additional patients.

Dermatology Times: What are the clinical implications of this study for the management of patients with advanced melanoma who are immune checkpoint inhibitor-naive? 

Prieto: The results from this study underscore the potential of lifileucel and pembrolizumab to evolve the frontline standard of care for patients with advanced melanoma. Currently, at least half of patients who receive front-line combination ICI therapy do not achieve long-term benefits, underscoring the need for novel early-line therapies to improve rate and depth of responses. The unprecedented response rates are highly encouraging for the anticipated results in our ongoing TILVANCE-301 trial, which is evaluating lifileucel in the same patient population to support accelerated and full U.S. approvals of lifileucel in combination with pembrolizumab in frontline advanced melanoma.

Dermatology Times: Are there any plans to investigate the combination of lifileucel and pembrolizumab in other cancer types or settings beyond advanced melanoma? 

Prieto: Yes, we are evaluating this combination regimen in other solid tumor cancers, including:

• In the IOV-COM-202 trial, we are evaluating lifileucel in combination with pembrolizumab in patients with head and neck cancer and non-small cell lung cancer (NSCLC). This trial is also assessing lifileucel in combination with ipilimumab and nivolumab in patients with NSCLC.
• The phase 2 C-145-04 trial is evaluating lifileucel in combination with pembrolizumab in patients with advanced cervical cancer.

More information on our clinical pipeline can be found here.

Reference

1. Iovance Biotherapeutics announces clinical data in frontline advanced melanoma at ASCO 2024 Annual Meeting. News release. Iovance Therapeutics. May 23, 2024. Accessed June 27, 2024. https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-data-frontline