Iovance plunges as it releases new clinical data for lifileucel in advanced melanoma

US late-stage biotech Iovance Biotherapeutics (Nasdaq: IOVA) has reported results from its C-144-01 clinical study in patients with advanced (unresectable or metastatic) melanoma who progressed on prior anti-PD-1/L1 therapy, and if BRAF mutation positive, also on prior BRAF or BRAF/MEK inhibitor therapy.

In registrational Cohort 4 (n=87), the objective response rate (ORR) by an independent review committee (IRC) using RECIST 1.1 criteria was 29% (95% confidence interval (CI): 19.5%, 39.4%) with three complete responses and 22 partial responses. The median duration of response (DOR) in Cohort 4 by IRC was 10.4 months with a median study follow-up of 23.5 months. These data demonstrate that one-time treatment with lifileucel therapy may provide meaningful benefit in heavily pre-treated patients. Cohort 4’s findings are supported by Cohort 2 (n=66), where the ORR by IRC was 35% (95% CI: 23.5%, 47.6%) with five complete responses and 18 partial responses. The median DOR in Cohort 2 was not reached with a median study follow-up of 36.6 months. The ORR by IRC for pooled patients (n=153) from both Cohorts 2 and 4 was 31% (95% CI: 24.1%, 39.4%) and median DOR was not reached at a median study follow up of 27.6 months.

Patients in Cohort 4 exhibited higher baseline disease burden in comparison to patients in Cohort 2, including a substantially higher proportion of patients with elevated baseline lactate dehydrogenase (LDH) levels, a well-known negative prognostic factor (64.4% versus 40.9%), as well as a greater number of tumor lesions at baseline (83.9% versus 65.2% with more than three lesions). In addition, patients in Cohort 2 also had approximately half the cumulative duration of anti-PD-1 therapy before lifileucel therapy in comparison to patients in Cohort 4. Reduced duration of prior anti-PD-1 therapy was shown 1 to be associated with an increase of DOR to lifileucel. The treatment-emergent adverse event profile in both cohorts was consistent with the underlying disease and known adverse event profiles of non-myeloablative lymphodepletion and interleukin-2 (IL-2) and was also consistent between Cohorts 2 and 4.