FDA Grants Novel TIL Therapy Breakthrough Therapy Designation for Advanced Cervical Cancer

The FDA has granted a breakthrough therapy designation to novel tumor-infiltrating lymphocyte therapy LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical cancer who have progressed on or after chemotherapy.¹

“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 CEO of Iovance, said in a statement. “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.”

The designation was granted as a result of preliminary data from the ongoing phase II innovaTIL-04 trial (NCT03108495). The open-label, multicenter trial is investigating the adoptive cell therapy with autologous tumor-infiltrating lymphocyte infusion followed by interleukin-2 for the treatment of patients with recurrent, metastatic, or persistent cervical cancer. A tumor sample is resected from each patient in the trial and All patients receive a preparative non-myeloablative lymphodepletion regimen prior to infusion.

The trial is expecting to enroll 59 patients who have been previously treated with 1 to 3 prior systemic chemotherapy regimens and have an ECOG performance status of 0 or 1. Previously, eligible patients had been allowed to have more prior treatment regimens, but the protocol were amended to limit the amount to a maximum of 3 prior therapies and to exclude patients who had received prior immunotherapy.

The primary endpoint of the study is objective response rate by RECIST v1.1 criteria, and secondary endpoints include duration of response, disease control rate, progression-free survival, overall survival, and adverse events.

Data from the phase II trial will be presented at the 2019 ASCO Annual Meeting.²According to the abstract, the preliminary objective response rate as of data cutoff was 44%, which consisted of 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, and 11 of 12 patients maintained their responses. Additionally, the safety profile was considered acceptable.

In February, LN-145 received a fast track designation from the FDA for the treatment of patients with recurrent, metastatic, or persistent cervical cancer who have progressed on or after chemotherapy. The agent is also being investigated for the treatment of patients with melanoma, head and neck cancer, and non—small cell lung cancer.

References:

1. Clovance Biotherapeutics Announces Breakthrough Therapy Designation for LN-145 for Treatment of Advanced Cervical Cancer Patients Who Have Progressed on or After Chemotherapy [press release]. San Carlos, CA: Iovance Biotherapeutics, Inc; May 22, 2019. https://bit.ly/2WnVTDd. Accessed May 23, 2019.
2. 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).