FDA Denies Approval of Retifanlimab for Locally Advanced or Metastatic SCAC Subgroup

The FDA issued a complete response letter to Incyte Corporation in response to the Biologics License Application for the PD-L1 inhibitor, retifanlimab (formerly MGA012), for the treatment of adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are intolerant of, platinum-based chemotherapy, according to a press release from the company.¹

In the letter, the FDA denied the approval of the agent for this indication. The FDA stated that more information is needed to prove the clinical benefit of retifanlimab in this SCAC patient group, which is consistent with a point raised by the Oncologic Drugs Advisory Committee (ODAC) during a meeting held on June 24, 2021. During the meeting, ODAC voted 13 to 4 against the approval of retifanlimab for patients with SCAC who have progressed on or who are intolerant of platinum-based chemotherapy.

“Patients with SCAC who have progressed after first-line chemotherapy currently do not have approved treatment options,” said Hervé Hoppenot, chief executive officer, Incyte. “While we are not surprised with the FDA decision given the ODAC recommendation, we are disappointed.”

The phase 2 PODIUM-202 clinical trial supported the BLA for retifanlimab. According to the most recent data, retifanlimab achieved durable responses in patients with previously treated locally advanced or metastatic SCAC.

In the 94 patients who were evaluated in the study, the objective response rate (ORR) was 13.8% (95% CI, 7.6-22.5) with the best overall response being a complete response in 1.1% of the population. Also, partial responses were observed in 12.8%, and stable disease was observed in 35.1%. Progressive disease was observed in 45.1% of patients, and 5.3% were not evaluable for response. These results led to a disease control rate (DCR) of 48.9%.²

Responses were seen in these patients regardless of gender, age, race, HIV status, liver metastasis, and PD-L1 status, according to a presentation given during the June ODAC meeting. Further, a decrease in tumor burden from baseline was seen in 46% of patients.

Survival-wise, the treatment led to a favorable 10.1-month median overall survival (OS).

Treatment-related adverse events (TRAEs) were seen in 59% of the patients. Twelve percent experienced grade 3 or higher TRAEs, and serious AEs were seen in 54%. Overall, treatment discontinuation occurred in 7% of patients, and 11% of patients experience a fatal AE.

Both immune-related endocrine and non-endocrine events were observed in the study population. Of those who had these immune-related events, the most common in each group was hypothyroidism and skin reactions, respectively. The safety observed with retifanlimab in PODIUM-202 was also deemed acceptable in the HIV-positive population and in those with PD-L1 expression.

PODIUM-202 (NCT03597295) enrolled patients who were aged 18 years of age or older with confirmed locally advanced or metastatic SCAC, who had disease progression on or after platinum-based therapy, as well as an ECOG performance status of 0 or 1, and measurable disease per RECIST v1.1. Patients who were HIV-positive were also eligible to enroll if they had a CD4-positive count ≥ 300 cells/μL, undetectable viral load, and receiving antiretroviral therapy.

The primary end point of the study was the ORR, and the secondary end points included duration of response, DCR, progression-free survival, OS, and the number of patients with TRAEs.

Currently, the study is ongoing at 47 locations across the United States. The Incyte Corporation plans to continue to explore retifanlimab for the treatment of cancer.

We remain committed to advancing science to find solutions for patients with unmet medical needs, and we will ensure close coordination with the FDA in order to address feedback and determine next steps for the review of retifanlimab," Hoppenot added.

_References:

_{1. Incyte provides regulatory update on retifanlimab for the treatment of certain patients with squamous cell carcinoma of the anal canal (SCAC). News release. Incyte Corporation. July 23, 2021. Accessed July 26, 2021. https://bit.ly/3rIkdwU}

_{2. June 24, 2021: Meeting of the Oncologic Drugs Advisory Committee Meeting. FDA website. June 24, 2021. Accessed June 26, 2021. https://bit.ly/3vVaIef}