Phase 3 Trial of Lifileucel/Pembrolizumab in Frontline Advanced Melanoma Begins


The safety and efficacy of the combination of lifileucel and pembrolizumab is being assessed in the phase 3 TILVANCE-301 among patients with untreated, unresectable, or metastatic melanoma.

Image Credit: Lisa []

Image Credit: Lisa []

About the Phase 3 TILVANCE-301 Trial

Trial Name: A Phase 3, Multicenter, Randomized, Open-label, Parallel Group, Treatment Study to Assess the Efficacy and Safety of the Lifileucel (LN-144, Autologous Tumor Infiltrating Lymphocytes [TIL]) Regimen in Combination With Pembrolizumab Compared With Pembrolizumab Monotherapy in Participants With Untreated, Unresectable or Metastatic Melanoma Identifier: NCT05727904

Sponsor: Iovance Biotherapeutics, Inc.

Recruitment Contact: Iovance Biotherapeutics Study Team, 866-565-4410,

Completion Date: March 1, 2030

The phase 3 TILVANCE-301 trial (NCT05727904) evaluating the tumor infiltrating lymphocyte (TIL) therapy, lifileucel (LN-144) in combination with pembrolizumab (Keytruda) vs pembrolizumab alone has randomized its first patient with frontline advanced, unresectable, or metastatic melanoma.1

“Our strategy is to offer TIL therapy across all lines of treatment for patients with advanced melanoma. Randomizing the first patient in TILVANCE-301, our first phase 3 trial at Iovance, is an important milestone. The trial offers TIL therapy as part of an earlier treatment approach for frontline advanced melanoma, while serving as a confirmatory trial to convert an accelerated approval to full approval for lifileucel in post-anti-PD-1 melanoma,” said Friedrich Graf Finckenstein, MD, chief medical officer of Iovance, in a press release.

Lifileucel is designed for patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable.

TILVANCE-301 trial builds on previous data reported with the use of TIL therapy in the early line for patients with advanced melanoma. Previously, the combination of lifileucel and pembrolizumab elicited an overall response rate of 67% ORR and durability of response, according to cohort 1A of the IOV-COM-202 trial (NCT03645928). These positive data have remained consistent in nearly 20 patients treated to date.

In May 2023, the FDA accepted the biologics license application and granted priority review for lifileucel for patients with advanced melanoma. A Prescription Drug User Fee Act action date of November 25, 2023, has been set for a decision on lifileucel as treatment of advanced melanoma.

The multicenter, randomized, open-label, phase 3 TILVANCE-301 trial will randomize approximately 670 patients to receive lifileucel in combination with pembrolizumab or pembrolizumab monotherapy with an optional crossover period.2 The primary end points of the study are objective response rate and progression-free survival, and the secondary end points to be assessed include overall survival, complete response rate, duration of response, event-free survival, and adverse events.

Patients are eligible for enrollment if aged 18-70 with histologically or pathologically confirmed diagnosis of stage IIIC, IIID, or IV unresectable or metastatic melanoma, an ECOG performance status of 0 or 1, an estimated life expectancy of > 6 months, at least 1 resectable lesion for lifileucel generation, at least 1 measurable disease, and adequate organ function.

Trial sites are actively enrolling adult patients in Florida and New Jersey with an estimated study completion date of March 1, 2030.

“TILVANCE-301 is expected to be well underway at the time of potential accelerated approval in this initial indication. This trial may also provide important insights into the Iovance platform approach for TIL and anti-PD-1 therapy combinations in additional solid tumors,” added Finckenstein, in the press release.1

1. Iovance Biotherapeutics announces first patient randomized in phase 3 TILVANCE-301 trial in frontline advanced melanoma. News release. Iovance Biotherapeutics, Inc. June 15, 2023. Accessed June 20, 2023.
2. Study to investigate lifileucel regimen plus pembrolizumab compared with pembrolizumab alone in participants with untreated advanced melanoma. Updated May 26, 2023. Accessed June 20, 2023.
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