FDA Approves Retifanlimab for Metastatic or Recurrent Locally Advanced Merkel Cell Carcinoma

This article originally appeared on our sister site, OncLive®.

The FDA has granted accelerated approval to retifanlimab-dlwr (Zynyz) for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).1

FDA logo on blue background

FDA logo on blue background

The regulatory decision is supported by data from the phase 2 POD1UM-201 trial (NCT03599713), in which retifanlimab elicited an objective response rate (ORR) of 52% (95% CI, 40%-65%) by independent central review (ICR) and RECIST v1.1 criteria in chemotherapy-naïve patients with metastatic or recurrent locally advanced MCC who had not previously received systemic therapy for their advanced disease (n = 65). Among those who responded to the agent, 18% achieved a complete response (CR) and 34% experienced a partial response (PR).

The duration of response (DOR) with retifanlimab ranged from 1.1 months to over 24.9 months. Notably, by the landmark analysis, 76% of patients continued to respond for at least 6 months, and 62% responded for 12 months or longer.

Continued approval of the agent may be contingent on verification and description of clinical benefit in confirmatory trials.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” Shailender Bhatia, MD, of University of Washington and Fred Hutchinson Cancer Center, stated in a press release. “The approval of Zynyz offers healthcare providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease, and I look forward to having Zynyz in our treatment portfolio for these difficult-to-treat patients.”

Retifanlimab, previously referred to as INCMGA00012, is a humanized IgG4 monoclonal antibody that targets human PD-1.2

The open-label, single-arm, multicenter, phase 2 trial enrolled patients with distant metastatic disease or recurrent, advanced locoregional disease that was not amenable to radiation or surgery, but was measurable by RECIST v1.1 criteria. Patients were required to be at least 18 years of age, have an ECOG performance status of 0 or 1, and tumor tissue available for central pathology review. In April 2020, enrollment was limited to patients who were chemotherapy naïve.

Patients could not have received prior systemic treatment for MCC or any treatment with anticancer agents, nor could they have participated in another interventional trial within 21 days before the first study dose. If patients received radiation within 2 weeks of their first study dose or radiation to the thoracic region at greater than 30 Gy within 6 months before their first study dose, they were excluded.

Other exclusion criteria include having known central nervous system metastases, interstitial lung disease, active noninfecious pneumonitis, or active autoimmune diseases requiring systemic immunosuppression beyond maintenance therapy.

Study participants were administered retifanlimab intravenously at a dose of 500 mg every 4 weeks until progressive disease, intolerable toxicity, or for up to 24 months. Investigators performed response assessments every 8 weeks for the first year of treatment and every 12 weeks thereafter.1

The primary objective of the trial was ORR per ICR utilizing RECIST v1.1 criteria, and key secondary end points comprised DOR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics.

Primary efficacy results from the chemotherapy-naïve cohort were shared during the 2021 SITC Annual Meeting.2 At a data cutoff of June 16, 2021, a total of 99 patients in this cohort received at least 1 dose of retifanlimab. In these patients, the median age was 71.0 years (range, 38-90). Most patients were male (66.7%), White (72.7%), and had an ECOG performance status of 0 (72.7%). Moreover, 36.4% of patients received previous radiotherapy and 67.7% had prior surgery.

The first 65 patients in this cohort were included in the primary efficacy analysis. For this full analysis set, the median follow-up was 7.5 months (range, 1.1-16.6). The median duration of treatment was 169.0 days (range, 1-708) and 57.6% of patients in this cohort were still receiving the agent.

At this time point, the ORR in this cohort with the agent was 50.8% (95% CI, 38.1%-63.4%), which comprised a CR rate of 16.9% and a PR rate of 33.8%; 20.0% had stable disease and 20.0% experienced disease progression. The DCR in this cohort was 60.0%. The median PFS was 13.8 months (95% CI, 7.4-not evaluable [NE]), and the median OR was not yet reached (95% CI, NE-NE). The median DOR had also not yet been reached (95% CI, NE-NE).

The safety population was comprised of 105 patients with MCC.1,3 The most common toxicities reported with the agent included fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, and nausea. Twenty-two percent of patients experienced serious adverse effects (AEs), with fatigue, arrhythmia, and pneumonitis cited as most frequently experienced.

Eleven percent of patients experienced AEs that led to permanent discontinuation of retifanlimab.


  1. Incyte announces FDA approval of Zynyz (retifanlimab-dlwr) for the treatment of metastatic or recurrent locally advanced Merkel cell carcinoma. News release. Incyte. March 22, 2023. Accessed March 22, 2023. https://investor.incyte.com/news-releases/
  2. Grignani G, Rutkowski P, Lebbe C, et al. 545 A phase 2 study of retifanlimab in patients with advanced or metastatic merkel cell carcinoma (MCC) (POD1UM-201). J Immunother Cancer. 2021;9(suppl 2). doi:10.1136/jitc-2021-SITC2021.545
  3. FDA grants accelerated approval to retifanlimab-dlwr for metastatic or recurrent locally advanced Merkel cell carcinoma. FDA. March 22, 2023. Accessed March 22, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
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