Rationale for Requested Change: On behalf of Incyte Corporation, I respectfully request the NCCN Anal Carcinoma Guidelines Panel review and consider the enclosed data for ZYNYZ® (retifanlimab-dlwr) for the treatment of adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who were not previously treated with systemic chemotherapy.
POD1UM-303/InterAACT 2 (NCT04472429) is a randomized, double-blind, multicenter, Phase III study evaluating the efficacy and safety of carboplatin-paclitaxel (CP) in combination with retifanlimab-dlwr or placebo in adults with inoperable, locally recurrent or metastatic SCAC who were not previously treated with systemic chemotherapy.[2]
Eligibility criteria included measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, no prior chemotherapy except as radiosensitizing treatment or (neo)adjuvant therapy if completed at least 6 months prior to study entry, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.[2] Patients with well-controlled HIV (i.e. CD4-positive cell count of at least 200 cells/microliter, undetectable viral load, and receiving antiretroviral therapy with no history of any HIV-related opportunistic infection for at least 4 weeks prior to study entry) were eligible. Previous treatment with PD-(L)1 directed therapy and active bacterial, fungal, or viral infections were exclusion criteria.
The primary endpoint was progression-free survival (PFS) by blinded independent central radiographic review.[2] Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.
A total of 308 patients were enrolled in the study (retifanlimab-dlwr plus CP [n=154], placebo plus CP [n=154]).[3] Median PFS was 9.3 months in the retifanlimab-dlwr plus CP group and 7.4 months in the placebo plus CP group (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47-0.84; p=0.0006). At interim analysis for OS, median OS in the retifanlimab-dlwr plus CP and placebo plus CP groups was 29.2 months and 23 months (HR, 0.70; 95% CI, 0.49-1.01; p=0.0273), respectively. The ORR was 56% (95% CI, 48-64) with retifanlimab-dlwr plus CP compared to 44% (95% CI, 36-52) with placebo plus CP (nominal p=0.0129). Median DOR was 14 months (95% CI, 8.6-22.2) and 7.2 months (95% CI, 5.6-9.3) among patients treated with retifanlimab-dlwr plus CP and placebo plus CP, respectively.
In POD1UM-303, the proportion of patients experiencing Grade 3 or higher treatment-emergent adverse events (TEAEs), Grade 5 TEAEs, serious adverse events (SAEs), treatment-related SAEs, and immune-related adverse events (AEs) was higher with retifanlimab-dlwr plus CP than with placebo plus CP.[3] The most common (greater than or equal to 10%) Grade 3 or higher TEAEs in the retifanlimab-dlwr plus CP group were neutropenia (35.1%), anemia (19.5%), and neutrophil count decreased (16.9%).
The following publications are submitted in support of this proposed change.
1. ZYNYZ [Prescribing Information] Wilmington, DE: Incyte.
2. Incyte Corporation. A Phase 3 global, multicenter, double-blind randomized study of carboplatin-paclitaxel with INCMGA00012 or placebo in participants with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal not previously treated with systemic chemotherapy (POD1UM-303/InterAACT 2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 September 16]. Available from: https://clinicaltrials.gov/show/NCT04472429 NLM Identifier: NCT04472429.
3. Rao S, Samalin-Scalzi E, Evesque L, et al. POD1UM-303/InterAACT 2: Phase 3 study of retifanlimab with carboplatin-paclitaxel in patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy [presentation]. Presented at: 2024 European Society for Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain.
We appreciate the Panel’s review and consideration of this submission. Should you have any questions or would like additional information, please do not hesitate to contact me.
Sincerely,
Danielle Janiszewski, PharmD
Associate Director, Medical Information
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