New Drug on the Fast Track for Melanoma Treatment

Maria Fardis, PhD

Maria Fardis, Ph.D.

A new drug may be on the way to treat patients with advanced melanoma, as the FDA granted LN-144, which is produced by Iovance Biotherapeutics, a fast track designation. The drug uses tumor-infiltrating lymphocyte (TIL) technology to bolster the body’s immune system to attack cancer cells.

The designation is based on data Iovance submitted from C-144-01, a phase 2 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 percent (four patients). Researchers observed tumor reduction in 77 percent 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 (out of body) expansion of TIL followed by lymphodepletion using fludarabine and cyclophosphamide, then infusion of TIL. Researchers administer up to six 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 two 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 two study arms.

Results from the study were first presented in a poster at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. The disease control rate was 64 percent (9/14) in these initial findings. At a median follow-up of 4.7 months, one patient had a complete response that last more than 15 months, three had a partial response and five 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 percent of patients had stage 4 disease. Nine patients (56.3 percent) 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 three (range, 1-6). All patients had received anti—PD-1 treatment, 14 had received anti-CTLA-4 treatment and two had received interleuken-2.

Nine patients (56.3 percent) experienced at least one grade 3 or higher treatment-emergent serious adverse events. The most common were febrile neutropenia (four patients), decreased neutrophil count (three patients) and decreased platelet count (three patients). 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 European Society for Medical Oncology (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, Ph.D., 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.