FDA Grants LN-144 Fast Track Status for Melanoma

Maria Fardis, PhD

Maria Fardis, PhD

The FDA has granted LN-144, an adoptive cell therapy that uses tumor-infiltrating lymphocyte (TIL) technology developed by Iovance Biotherapeutics, a fast track designation for the treatment of patients with advanced melanoma.

The designation is based on data Iovance submitted from C-144-01, a phase II multicenter study. Efficacy data for 14 of the 16 patients who were treated showed that LN-144 induced an overall response rate (ORR) of 29% (n = 4). Researchers observed tumor reduction in 77% of patients.

The purpose of the FDA’s fast track designation is to accelerate the development and regulatory review of drugs intended to treat serious conditions and fill an unmet medical need. The designation allows for a rolling review of a company’s biologic license application.

Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL followed by lymphodepletion using fludarabine and cyclophosphamide, then infusion of TIL. Researchers administer up to 6 doses of IL-2 (600,000 IU/kg) to support multiplication of TIL and engraftment.

C-144-01 is still recruiting, with the goal of enrolling 60 patients into 2 cohorts. In the first cohort, patients will receive noncryopreserved TIL product to be administered to patients, while patients in cohort 2 will receive a cryopreserved product. Eventually, researchers plan to add a third cohort retreating patients from the first 2 study arms.

Results from the study were first presented in a poster at the 2017 ASCO Annual Meeting. The disease control rate was 64% (9/14) in these initial findings. At a median follow-up of 4.7 months, 1 patient had a complete response that last more than 15 months, 3 had a partial response, and 5 had stable disease. Four patients progressed while on treatment. Median time to first response was 1.6 months.

The median age of all 16 treated patients was 54.5 years (range, 41-72). Patients also displayed a high tumor burden at baseline. The median sum of diameter for target lesions was 10.2 cm, and 81% of patients had stage 4 disease. Nine patients (56.3%) had BRAF mutations. Researchers said that BRAF status did not appear to play a role in efficacy.

Patients were highly refractory to multiple prior therapies. The median number of prior therapies was 3 (range, 1-6). All patients had received anti—PD-1 treatment, 14 had received anti-CTLA-4 treatment, and 2 had received interleuken-2.

Nine patients (56.3%) experienced at least 1 grade ≥3 treatment-emergent serious adverse events . The most common were febrile neutropenia (n = 4), decreased neutrophil count (n = 3), and decreased platelet count (n = 3). One patient died due to progression before the first tumor assessment.

LN-144 is also being investigated as a treatment for recurrent/metastatic squamous cell carcinoma of the head and neck and recurrent/metastatic or persistent cervical cancer. Iovance plans to present data assessing LN-144 as a treatment for non-Hodgkin lymphoma during a poster session at the 2017 ESMO Congress in September.

“As we explore potential utilization of TIL in treatment of multiple cancer types, we [will] present data at ESMO that demonstrate the ability to produce TIL from lymphoma that have similar functionality as TIL generated from melanoma, giving us reason to further explore the potential of our TIL cell therapy for lymphoma patients in the future,” Iovance CEO Maria Fardis, PhD, said in a press release.

“Leveraging our experience in TIL generation from solid tumors to blood-born cancers is a natural extension of our learnings to date. We are exploring potential collaborations with lymphoma experts to supplement our research efforts. The data to be presented at ESMO is indicative of our efforts in becoming a leader in TIL treatment for a variety of tumor types,” added Fardis.

Sarnaik A, Kluger HM, Chesney JA, et al. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. J Clin Oncol 35, 2017. (suppl; abstr 3045).