On October 11, 2018 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported results from an FDA End of Phase 2 meeting and provided a corporate update (Press release, Iovance Biotherapeutics, OCT 11, 2018, View Source;p=RssLanding&cat=news&id=2371343 [SID1234530323]).

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The company reported that an End of Phase 2 meeting with the FDA was held. FDA has acknowledged the potential acceptability of a single-arm cohort for registration. FDA has further acknowledged that conduct of a randomized Phase 3 trial may not be feasible in its intended population of advanced melanoma patients who have been treated with at least one systemic therapy including a PD-1 blocking antibody and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor and is not required for initial registration of lifileucel. A new cohort of 80-100 patients in C-144-01 will be enrolled with a prospective definition of the primary endpoint of ORR to be read out by a Blinded Independent Review Committee (BIRC) to support registration of lifileucel. This new cohort, which the company refers to as Cohort 4, will be initiated in early 2019 and is expected to be fully enrolled by late 2019/early 2020. BLA submission to FDA is expected in the second half of 2020.

The company also reported that Iovance was granted a Regenerative Medicine Advanced Therapy (RMAT) designation for lifileucel in advanced melanoma based on data provided to the U.S. Food and Drug Administration (FDA) from the company’s C-144-01 study. RMAT designation is granted for regenerative medicine drugs and allows for increased access to FDA during development. Under this designation, surrogate endpoints can be used to receive approval for a product, accelerated approval may be granted, and a rolling review of a Biologics License Application (BLA) may be possible for the Center for Biologics Evaluation and Research (CBER).

"We are very excited with the progress made at Iovance during 2018. Specifically, we are pleased to have alignment with FDA regarding acceptability of a single-arm cohort to support registration of our lead product. In addition, we have greatly optimized our manufacturing process with Gen 2, leading to a scalable, commercial manufacturing process. We now have a global footprint with our clinical sites resulting in increased clinical enrollment and have produced sufficient data to discuss our registration path with FDA. As part of the recent interactions, we have also received an RMAT designation allowing for more frequent interactions with the FDA, benefiting from the agency’s guidance during development of lifileucel," said Dr. Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance Biotherapeutics.

Corporate Update

Regulatory

Iovance held an End of Phase 2 meeting with FDA during which the agency acknowledged that a single-arm cohort as part of C-144-01 could be supportive of initial registration and conduct of a randomized Phase 3 trial in the patient population being enrolled may not be feasible.
Iovance was granted an RMAT designation for advanced melanoma.
Iovance intends to continue consultation with FDA under the RMAT designation and enroll a new cohort of patients to support registration of lifileucel. The new cohort will have a prospective definition of the primary endpoint of ORR by BIRC and release criteria for lifileucel.
Clinical

The Company also reported that data from 46 patients of Cohort 2 of trial C-144-01 will be provided at SITC (Free SITC Whitepaper) 2018. For these 46 patients, an objective response rate (ORR) of 37% has been observed in the cohort, with duration of response (DOR) ranging from 1.3+ to 14+ months depending on time of enrollment. The ORR includes one (1) complete response and 16 partial responses, six (6) of which are unconfirmed and pending patient’s upcoming second assessments.
Enrollment in the global Phase 2 metastatic melanoma study, C-144-01, has reached the predefined sample size. Enrollment into the existing Cohort 2 will be closed and a new Cohort 4 will be initiated in early 2019. The company plans on initiating enrollment into Cohort 4 in early 2019 and expects to fully enroll the necessary patients into Cohort 4 by late 2019/early 2020.
BLA submission is expected in the second half of 2020.
Enrollment continues in other Iovance studies. Patient dosing in EU was initiated in the C-145-04 study of cervical carcinoma. The study design is based on Simon’s two-stage design. Stage one has now been completed and enrollment in the study continues. To date, preliminary data for 15 patients yields an ORR of 27% with an early look at the DOR ranging from 2.4 to 2.5+ months. In the C-145-03 study of head and neck cancer, to date, preliminary data for 13 patients yields an ORR of 31% with a DOR ranging from 2.8 to 7.6 months. The safety findings from these studies remain consistent with previous reports.
Data referenced above is from a data cut as of October 4, 2018.
Manufacturing

In support of the ongoing studies in EU, in addition to Lonza, Netherlands, a second European manufacturing collaboration was initiated.
IP

Two U.S. patent applications covering therapeutic methods based upon Generation 2 manufacturing, developed at Iovance, have been recently allowed.