FDA Grants LN-145 Breakthrough Designation for Cervical Cancer

The FDA has granted a breakthrough therapy designation to the tumor-infiltrating lymphocyte (TIL) therapy LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical cancer with disease progression on or after chemotherapy, according to Iovance Biotherapeutics, the manufacturer of the treatment.

The designation is based on data from the ongoing phase II innovaTIL-04 (C-145-04) trial, the latest results of which are scheduled to be presented in June at the 2019 ASCO Annual Meeting. Data in an abstract released ahead of the meeting showed that the TIL therapy had an overall response rate (ORR) of 44% in patients with advanced cervical cancer.

“We are very excited that the FDA has granted LN-145 in advanced cervical cancer breakthrough therapy designation. Cervical cancer patients who have progressed on or after chemotherapy have limited treatment options. We hope to bring LN-145 to these patients as quickly as possible,” Maria Fardis, PhD, MBA, president and chief executive officer of Iovance, said in a press release.

“The designation allows us to expedite our development program through more frequent interactions with the FDA and provides eligibility for rolling review and priority review,” added Fardis.

The ongoing, open-label, multicenter phase II C-145-04 study accrued patients with advanced cervical cancer who received ≥1 line of chemotherapy. Patients who had been previously treated with an immune checkpoint inhibitor were excluded from enrollment.

The manufacturing of LN-145 involves a 22-day process whereby TILs are generated at GMP facilities from tumors that have been shipped from local sites where they were initially harvested. The final LN-145 TIL treatment is cryopreserved and shipped back from the GMP to the original site where the patient is being treated.

Patient treatment involves preconditioning lymphodepletion (cyclophosphamide, fludarabine) for 1 week, followed by a single LN-145 infusion, and then up to 6 doses of IL-2 (600,000 IU/kg). The primary endpoint was ORR (RECIST 1.1), with secondary outcome measures including duration of response, disease control rate, and safety.

At the data cutoff of February 4, 2019, there were 27 evaluable patients. The mean age was 47 years and patients had received a mean of 2.6 prior lines of therapy. The mean number of TIL cells infused was 28 x 10⁹, patients received a median of 6 doses of IL-2.

The 44% (n = 12) ORR included 1 complete response, 9 partial responses, and 2 unconfirmed partial responses. The disease control rate was 89%. At a median follow-up of 3.5 months, 11 of the 12 responding patients maintained their response.

“The adverse event profile was generally consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens,” first author Amir A. Jazaeri, Director of the Gynecologic Cancer Immunotherapy Program in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center, and coauthors wrote in their ASCO abstract.

Jazaeri et al explained in their abstract that the ORR for second-line treatment with chemotherapy or immunotherapy in advanced cervical cancer ranges between 4% and 14%. Now that TILs have shown durable responses in some patients, the researchers hope this treatment can deliver on the promise of long-term disease control.

For more on the emergence of TILs in oncology, read our OncLive exclusive.

Jazaeri AA, Zsiros E, Amaria RN, et al. Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma. J Clin Oncol. 2019;37 (suppl; abstr 2538).