INDICATIONS

Squamous cell carcinoma of the anal canal (SCAC)
The first and only approved PD-1 inhibitor for SCAC1,2
ZYNYZ, in combination with carboplatin-paclitaxel, is indicated for the first-line treatment of adults with inoperable, locally recurrent or metastatic SCAC.1
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Merkel Cell
Carcinoma (MCC)
ZYNYZ is indicated as monotherapy for the first-line treatment of adult patients with metastatic or recurrent locally advanced MCC not amenable to curative surgery or radiation therapy.1
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SCAC

POD1UM-303 STUDY2

POD1UM-303/InterAACT 2 was a randomised, multicentre, double-blind, phase 3 trial in 308 adult patients with chemotherapy-naïve metastatic or inoperable locally recurrent SCAC that compared ZYNYZ or placebo in combination with carboplatin-paclitaxel.

KEY ELIGIBILITY CRITERIA2

  • Adults with inoperable, locally recurrent or metastatic SCAC
  • No prior chemotherapy, except as radiosensitising treatment or (neo)adjuvant therapy ≥6 months prior to study entry
  • Patients with HIV and well-controlled infection were eligible

PRIMARY ENDPOINT2

  • PFS per BICR*

KEY SECONDARY ENDPOINT2

  • OS

OTHER SECONDARY ENDPOINTS2

  • ORR, DOR, DCR, safety

EFFICACY2

  • POD1UM-303 met its primary endpoint, achieving a significant increase in median PFS compared with current SOC in 1L locally recurrent or metastatic SCAC

SAFETY2

  • ZYNYZ plus carboplatin–paclitaxel was generally well tolerated
  • Serious adverse reactions occurred in 47.4% of patients receiving ZYNYZ plus carboplatin-paclitaxel and 38.8% of patients receiving placebo plus carboplatin-paclitaxel
  • Results are consistent with the extensive data for other combinations of platinum-based chemotherapy with PD-(L)1 inhibitors

MCC

POD1UM-201 STUDY3

The efficacy and safety of ZYNYZ was studied in the POD1UM-201 study, an open-label, single-arm, multiregional study that enrolled patients with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease.

Patients received ZYNYZ 500 mg every 4 weeks until disease progression or unacceptable toxicity, for a maximum of 2 years.

KEY ELIGIBILITY CRITERIA3

  • Patients with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease
  • Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible
  • Patients who were HIV-positive, with an undetectable viral load, a CD4+ count ≥300 cells/μL and receiving antiretroviral therapy were eligible

MAJOR EFFICACY OUTCOMES3

  • The major efficacy outcomes were ORR and DOR as assessed by an independent central review committee

EFFICACY3

  • POD1UM-201 met its primary endpoint (ORR)
ENDPOINT ZYNYZ (n=101)
ORR, %
Objective response rate (95% CI) 54.5 (44.2, 64.4)
Complete Response 17.8
Partial response 36.6
DOR, MONTHS
Median (95% CI) NR (22.9, NE)
Minimum, maximum 1.1, 55.3

SAFETY3

  • ZYNYZ monotherapy has a safety profile that is representative of the PD-(L)1 inhibitor class
  • Most common immune-related AEs were skin reactions (9.9%) and hypothyroidism (7.9%); 10.9% of patients had grade ≥3 immune-related AEs and 8.9% discontinued treatment due to immune-related AEs
▼This product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Please see the full ZYNYZ (retifanlimab) Summary of Product Characteristics for further information.
*Defined as the time from the date of randomisation until disease progression according to RECIST v1.1 by BICR or death due to any cause. **Based on stratified Cox model.
1L, first line; AE, adverse event; BICR, blinded independent central review; CD, cluster of differentiation; CI, confidence interval; DCR, disease control rate; DOR, duration of response; HIV, human immunodeficiency virus; HR, hazard ratio; NE, not evaluable; NR, not reached; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PFS, progression-free survival; RECIST, response evaluation criteria in solid tumours; SCAC, squamous cell carcinoma of the anal canal; SOC, standard of care.
REFERENCES
1. ZYNYZ® (retifanlimab) Summary of Product Characteristics. Incyte. 2. Rao S, et al. Lancet. 2025;405:2144–52. 3. Grignani G, et al. J Immunother Cancer. 2025;13:e012478.