Retifanlimab-dlwr (Zynyz)
is a programmed death receptor-1 (PD-1)-blocking monoclonal antibody.
Programmed death receptors are present on T cells, part of the body's immune
system. If they bind to the PD ligands, PD-L1 and PD-L2, that are found on tumor
cells, they prevent the T cells from surveilling and killing tumor cells.
Blocking the binding of the ligands to the programmed death receptors allows
the T cells to remain active and perform their surveillance and killing of
tumors.
ANAL
CARCINOMA
Anal
carcinoma is a rare type of cancer that begins in the tissues of the anus, the
opening at the end of the digestive tract. Most cases are a specific subtype
called squamous cell carcinoma of the anal canal (SCAC), which makes up about
80 percent of all anal cancers. A major cause of anal carcinoma is long‑term infection with human papillomavirus (HPV). About 90 percent of anal squamous cell tumors are HPV‑positive. Anal carcinoma can often be treated successfully
when found early, but advanced disease can be more difficult to treat.
CLINICAL
TRIALS
First-line
treatment
The safety
and efficacy of retifanlimab-dlwr (Zynyz), in combination with carboplatin and
paclitaxel, were evaluated in a multicenter, randomized, double‑blind, phase III clinical trial (POD1UM‑303; NCT04472429) in individuals with inoperable, locally
recurrent or metastatic squamous cell carcinoma of the anal canal, who were chemotherapy
naive. A total of 308 participants were enrolled and randomly assigned 1:1 into two
cohorts. The first cohort of 154 individuals received intravenous (IV) retifanlimab-dlwr (Zynyz) plus carboplatin and paclitaxel. The second cohort of 154
individuals received placebo plus carboplatin and paclitaxel. Individuals in cohort 1 continued to receive
treatment, for up to 1 year, or until there was disease progression,
unacceptable toxicity, withdrawal of consent, or death. Individuals in cohort 2
could receive single-agent retifanlimab-dlwr (Zynyz) upon disease progression,
if desired. The primary endpoint was progression‑free survival (PFS). Key secondary endpoints included
overall survival (OS), overall response rate (ORR), duration of response (DOR),
and safety.
The median
PFS in the retifanlimab-dlwr (Zynyz) cohort was 9.3 months (95 percent confidence interval [CI], 7.5–11.3
months) compared with 7.4 months (95 percent CI, 7.1–7.7 months) in the placebo cohort
(hazard ratio [HR] 0.63 [95 percent CI, 0.47–0.84]; P=0.0006). Median OS was 29.2
months (95 percent CI, 24.2 months to not estimable [NE]) for the retifanlimab-dlwr
(Zynyz) cohort versus 23.0 months (95 percent CI, 15.1–27.9 months) for placebo (HR
0.70; P=0.027). ORR was 55.8 percent (95 percent CI, 47.6–63.8 percent) with retifanlimab-dlwr
(Zynyz) compared with 44.2 percent (95 percent CI, 36.2–52.4 percent) with placebo (nominal P=0.013). Median DOR was 14.0 months (95 percent CI, 8.6–22.2 months) in the retifanlimab-dlwr
(Zynyz) cohort versus 7.2 months (95 percent CI, 5.6–9.3 months) in the placebo
cohort. There were four fatal adverse events in the retifanlimab-dlwr (Zynyz)
cohort, but only one was considered to be treatment related. There was one
fatal adverse event in the placebo cohort that was not considered to be
treatment related. Although there was a higher rate of grade 3 or worse adverse
events in the retifanlimab-dlwr (Zynyz) cohort versus the placebo cohort, the
toxicities were manageable with standard care.
Second-line
and subsequent therapy
The safety
and efficacy of retifanlimab-dlwr (Zynyz) was
studied in a phase II, open-label, multicenter clinical trial (POD1UM-202;
NCT03597295). Study participants included 94 individuals with locally advanced
or metastatic squamous cell anal cancer whose disease had progressed on or
after platinum‑based
chemotherapy, or were ineligible for or intolerant to platinum-based
chemotherapy. Participants received retifanlimab-dlwr (Zynyz) 500 mg IV every 4 weeks, for a maximum of 2 years, or until
there was disease progression, unacceptable toxicity, or discontinuation. The
primary endpoint was ORR. Key secondary endpoints included DOR, PFS, and OS.
The ORR
was 13.8 percent (95 percent CI, 7.6–22.5 percent), including one complete and 12 partial
responses. The median DOR was 9.5 months (95 percent CI, 5.6 months to NE). The median
PFS was 2.3 months (95 percent CI, 1.9–3.6 months). The median OS was 10.1 months
(95 percent CI, 7.9 months to NE). Side effects were common but generally manageable, with
the safety profile consistent with other PD‑1 inhibitors.
MERKEL
CELL CARCINOMA
Merkel
cell carcinoma (MCC) is a rare, highly aggressive form of skin cancer that
usually develops on sun-exposed areas of the body. It often affects older
adults, and usually those with light skin coloration. Individuals with immune
deficiency are at a higher risk of developing MCC. MCC is prone to locoregional
recurrence and distant metastasis. Recurrence of MCC is associated with a poor
prognosis. The 5-year survival of individuals with metastatic disease is 13.5
percent.
CLINICAL
TRIAL
The safety and efficacy of
retifanlimab-dlwr (Zynyz) was studied in a phase II, nonrandomized, open-label,
multicenter clinical trial (POD1UM-201; NCT03599713). Study participants
included 101 individuals
with treatment-naïve MCC that was metastatic or advanced locally recurrent. The participants received
retifanlimab-dlwr (Zynyz) 500 mg as an IV infusion every 4 weeks until
disease progression, unacceptable toxicity, or up to 24 months. The primary
outcome measure was ORR. Key secondary outcome measures were DOR, PFS, OS, and safety.
The ORR was 55 percent (95 percent CI, 44–64 percent) with 18 (18 percent) complete responses and 37 (37 percent) partial responses. The median DOR was not reached (95 percent CI, 14.0 months to NE) for
individuals achieving a complete response and was 25.3 months (95 percent CI, 14.2
months to NE) for individuals with a partial response. At the time of data cutoff, the median PFS was 54 percent (95 percent CI, 43–63 percent). At the time of data cutoff, the median OS was not yet
reached, but 63 percent of participants were still alive at 3 years. The safety
profile was consistent with other PD-1 inhibitors.
OFF-LABEL INDICATIONS
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
