Iovance is on track to complete its rolling BLA submission for lifileucel in the post-anti-PD1 melanoma indication in the first quarter of 2023.
Iovance Biotherapeutics’ tumor infiltrating lymphocyte (TIL) therapy lifileucel is creeping closer to clinic for treating both advanced melanoma and metastatic non-small cell lung cancer, according to a recent update from the company.1
After discussions with the FDA in the fourth quarter of 2022, Iovance announced the phase 3, confirmatory, TILVANCE-301 study that will investigate lifileucel in combination with pembrolizumab in 670 randomized patients with frontline advanced melanoma compared to pembrolizumab monotherapy. The study’s primary endpoints of objective response rate (ORR) and progression free survival will be used to support approval of the therapy’s biologics license application (BLA) in both frontline advanced melanoma and post-anti-PD-1 therapy advanced melanoma
After initiating in August 2022, Iovance had previously expected to complete the rolling BLA submission for lifileucel for unresectable or metastatic melanoma that progressed on or after prior anti-PD-1/L1 therapy, and if BRAF mutation positive, also prior BRAF or BRAF/MEK inhibitor therapy, by the end of 2022, however, this was pushed back to, and remains on track for, the first quarter of 2023.2 The delay came after the FDA requested supplemental validation information and comparability data for the therapy.
“We continue to make substantial progress with our ongoing BLA submission and remain close to the finish line. The FDA has provided recent valuable feedback to the IND application and remains supportive during the rolling BLA submission process. Iovance is fully committed to securing FDA approval as soon as possible to deliver the first individualized, 1-time cell therapy for advanced melanoma patients, who have a significant unmet medical need,” Frederick Vogt, PhD, JD, interim president and chief executive officer, Iovance, said in a statement.2
In the frontline advanced melanoma indication, Iovance announced positive data on lifileucel in combination with pembrolizumab from 20 participants treated in cohort 1A of the IOV-COM-202 phase 2 trial (NCT03645928).1 The data were consistent with that previously reported, with robust and durable ORRS. More detailed data will be shared later in 2023.
Iovance also shared data from cohort 3A of patients with non-small cell lung cancer (NSCLC) of the IOV-COM-202 trial, including an ORR of 47% (n =8) in treated patients, with responses observed regardless of PD-L1 status. The study is continuing to enroll,and safety findings have been consistent with findings of Iovance’s other TIL therapy/pembrolizumab combinations.
In this cohort, response rates were highest in patients who had treatment-naïve disease (80% ORR; n = 4) or post-chemotherapy anti-PD-1-naïve disease (43% ORR; n = 3) and lower in patients with EGFR-mutant disease after prior treatment with tyrosine kinase inhibitors (TKI; 20% ORR; n = 1). Two patients, 1 with post-chemotherapy anti-PD-1 naïve disease and 1 with EGFR-mutant disease after prior treatment with TKI, achieved complete responses and remain in the study. More data will be presented at future medical meetings.
The results and sub analyses will inform a future registration trial of lifileucelin patients with NSCLC, which Iovance plans to meet with the FDA about in 2023. Iovance plans to propose a registration trial in patients with frontline, advanced, EGFR wild-type NSCLC that will be a frontline maintenance study of standard-of-care pembrolizumab and limited duration chemotherapy followed by lifileucel and pembrolizumab combination therapy compared with pembrolizumab monotherapy in responding patients.