Drugs Xagena
The U.S. Food and Drug Administration ( FDA ) has approved Zynyz ( Retifanlimab-dlwr; Retifanlimab ), a humanized monoclonal antibody targeting programmed death receptor-1 ( PD-1 ), for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma ( MCC ).
The Biologics License Application ( BLA ) for Zynyz for this indication has been approved under accelerated approval by the U.S. FDA based on tumor response rate and duration of response. Continued approval of Zynyz for this indication may be contingent on verification and description of clinical benefit in confirmatory trials.
Merkel cell carcinoma is a rare and aggressive type of skin cancer that frequently appears as a single, painless, reddish-purple skin nodule on the head, neck and arms in skin exposed to sunlight.
Merkel cell carcinoma tends to grow quickly and has a high rate of metastatic disease, leading to a poor prognosis.
The estimated five-year overall survival ( OS ) rate is 14% in patients with Merkel cell carcinoma who present with distant metastatic disease.
Merkel cell carcinoma impacts less than 1 per 100,000 people in the U.S., but incidence rates are rapidly rising, especially in adults over the age of 65.
More than a third of patients with Merkel cell carcinoma present with regional or distant metastases, which are associated with high rates of mortality.
The FDA approval was based on data from POD1UM-201, an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced Merkel cell carcinoma who had not received prior systemic therapy for their advanced disease.
Among chemotherapy-naïve patients ( n=65 ), Zynyz monotherapy resulted in an objective response rate ( ORR ) of 52% ( 95% confidence interval [ CI ]: 40-65 ) as determined by independent central review ( ICR ) using RECIST v1.1. Complete response was seen in 12 patients ( 18% ), and 22 patients ( 34% ) showed partial response. Among the responding patients, the duration of response ( DoR ) ranged from 1.1 to 24.9+ months, and 76% ( 26/34 ) experienced a duration of response of 6 months or longer, and 62% ( 21/34 ) experienced a duration of response of 12 months or longer by landmark analysis.
Serious adverse reactions occurred in 22% of patients receiving Zynyz. The most frequent serious adverse reactions ( greater than or equal to 2% of patients ) were fatigue, arrhythmia and pneumonitis.
Permanent discontinuation of Zynyz due to an adverse reaction occurred in 11% of patients.
The most common ( greater than or equal to 10% ) adverse reactions that occurred in patients receiving Zynyz were fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia and nausea.
In POD1UM-201 patients received Zynyz 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, for up to 24 months. Tumor response assessments were performed every eight weeks for the first year of therapy and 12 weeks thereafter.
The primary endpoint was objective response rate as determined by independent central radiographic review using RECIST v1.1. Secondary endpoints included duration of response, disease control rate ( DCR ), progression-free survival ( PFS ) and overall survival; safety and pharmacokinetics. ( Xagena )
Source: FDA, 2023
XagenaMedicine_2023
