A lower objective response rate in cohort 4 reflected a higher disease burden with a greater number of tumors.
Iovance Biotherapeutics’ tumor infiltrating lymphocyte therapy (TIL) lifileucel (LN-144) has shown promising clinical results in patients with advanced melanoma, according to updated data from the C-144-01 clinical study (NCT02360579).
New data from cohort 4 (n = 87) of the study revealed a 29% overall response rate (ORR; 95% CI, 19.5-39.4), in patients with unresectable or metastatic melanoma who progressed on prior anti-PD-1/L1 therapy, and if BRAF+, also on prior BRAF or BRAF/MEK inhibitor therapy.
“We are pleased to report positive results for lifileucel from the registrational Cohort 4 data from the C-144-01 study. Iovance is proceeding towards submission of a BLA in August 2022 using these results as well as the potentially supportive results from Cohort 2 of the C-144-01 study,” Frederick Vogt, PhD, interim president and chief executive officer, Iovance, said in a statement. “We thank our patients, their families, and our investigators, employees, shareholders, and advocates for their support. We look forward to reporting further progress with our lifileucel BLA and launch preparations in 2022.”
Investigators found that participants in cohort 4 had 3 complete responses (CRs) and 22 partial responses (PRs). The median duration of response (DOR) in Cohort 4 by an independent review committee (IRC) was 10.4 months with a median follow-up of 23.5 months.
These findings build off of earlier positive findings in cohort 2 (n = 66), in which ORR was 35% (95% CI, 23.5-47.6) with 5 CRs and 18 PRs. Median DOR was not reached with a median follow-up was 36.6 months. Overall, ORR for participants in cohorts 2 and 4 was 31% (95% CI, 24.1-39.4) and median DOR was not reached with a median follow-up of 27.6 months.
Comparing the baseline demographics of participants in cohort 4 to cohort 2 revealed a higher baseline disease burden as well as a substantially higher proportion of patients with elevated baseline lactate dehydrogenase (LDH) levels (64.4% vs 40.9%). Participants in cohort 4 also had a greater number of tumor lesions at baseline (83.9% vs 65.2% with more than 3 lesions). Patients in cohort 2 also had around half the cumulative duration of anti-PD-1 therapy prior to lifileucel therapy, a reduction of which has been associated with an increase of DOR to lifileucel.
Lifileucel was well-tolerated, with a treatment-emergent adverse event (AE) profile consistent with underlying disease in both cohorts. Other AEs were consistent with non-myeloablative lymphodepletion and interleukin-2 (IL-2) therapy and were consistent between cohorts.
“Treatment of melanoma patients after failure of anti-PD-1 therapy remains a critical unmet medical need without an approved therapeutic option. Available care for metastatic melanoma patients in this setting is chemotherapy, which has been reported to offer a four to ten percent response rate with a very short median duration of response. We are excited about the results from registrational Cohort 4 of the C-144-01 study and the potential of lifileucel as a new treatment option for these patients,” Friedrich Graf Finckenstein, MD, chief medical officer, Iovance, added to the statement.
Additional data from cohorts 2 and 4 will be presented at a scientific meeting in the second half of 2022. Using these data, the planned BLA submission for lifileucel in advanced melanoma remains on track for August 2022.