Zynyz (retifanlimab-dlwr) / Incyte, MacroGenics, Sagard Healthcare, Knight Therap - LARVOL DELTA

Efficacy and safety of retifanlimab in gastrointestinal malignancies: A systematic review of clinical trials. (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Review • Gastrointestinal Cancer • Oncology

Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Washington University School of Medicine | N=12 ➔ 27

Enrollment change • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

Immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis: Disproportionality analysis from FAERS (ESMO-IO 2025) - "Cases were grouped by PD-1 inhibitors (pembrolizumab, nivolumab, cemiplimab, sintilimab, tislelizumab, camrelizumab, retifanlimab, toripalimab) and PD-L1 inhibitors (atezolizumab, durvalumab, avelumab). Clinicians should remain vigilant for HLH—especially early fever, cytopenias, and rising ferritin—and seek prompt hematology input with diagnostic workup, which may be lifesaving. Differences may reflect pharmacodynamics, indication mix, combinations, and reporting bias; prospective, mechanism-focused studies are needed to clarify causality and guide mitigation strategies.Legal entity responsible for the study The authors."

Checkpoint inhibition • Breast Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Survival Results of Phase II Bria-IMT Allogenic Whole Cell-Based Cancer Vaccine (SABCS 2025) - P1/2, P3 | "Coadministration w/ an anti-PD-1 CPI, the vaccine response is reinforced, counteracting the immuno-suppressive tumor microenvironment.MethodsThis phase I/II study evaluated the Bria-IMT regimen: low-dose cyclophosphamide (Day –2) followed by SV-BR-1-GM and CPI (pembrolizumab or retifanlimab), then low-dose local peg- interferon α. On basis of these results, a randomized phase III trial comparing the Bria-IMT regimen to physician's choice is ongoing (NCT06072612). Trial information: NCT03328026."

IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Triple Negative Breast Cancer • CTCs • HER-2 • IFNG • PD-L1 • PGR

Survival outcomes in POD1UM-303/InterAACT-2: A phase III study of retifanlimab (R) + carboplatin-paclitaxel (CP) in first-line (1L) advanced squamous anal cancer (SCAC) (ESMO-IO 2025) - P3 | "Safety was consistent with previous reports of this study and other PD-(L)1 studies.Conclusions Retifanlimab provided meaningful clinical benefit when added to 1L chemotherapy for advanced SCAC and is a new therapeutic option for this rare and difficult to treat disease. Table: 123MO Overall survival subgroup analysis *Includes unknown and/or missing Clinical trial identification NCT04472429.Legal entity responsible for the study Incyte Corporation, Wilmington, USA."

Clinical • Metastases • P3 data • Anal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Retifanlimab and Epacadostat in Combination With Radiation and Bevacizumab in Patients With Recurrent Gliomas (clinicaltrials.gov) - P2 | N=51 | Completed | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ Oct 2025

Trial completion • Trial completion date • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Tumor and Immune Dynamics Following Sequential CDK4/6 and PD-1 Inhibition: Results from a Phase 2 Study in Dedifferentiated Liposarcoma. (PubMed, Cancer Res Commun) - "A palbociclib lead-in prior to retifanlimab had a high rate of immune-related toxicities. Correlative analyses identified changes in tumor and immune cells attributable to treatment. A study of concurrent dosing of the combination is ongoing."

IO biomarker • Journal • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor • CD38 • CD4 • ICOS • LAG3

Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2028 ➔ Oct 2030 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Real-World Evidence on Treatment Patterns and Guidelines in Patients With Advanced Merkel Cell Carcinoma Across the US and Europe (ISPOR-EU 2025) - "Immunotherapies (avelumab, pembrolizumab, retifanlimab, and nivolumab) are the first-line agents recommended for aMCC by both NCCN and ESMO guidelines...Similar trends were observed in Europe, with immunotherapy used as 1L treatment in 89%-100% of patients across studies, and chemotherapy (cisplatin/carboplatin + etoposide) used in 11%-59.6% of cases prior to avelumab. Real-world treatment patterns for aMCC are largely consistent with guidelines across the US and Europe, reflecting increased use of immunotherapy as a first-line treatment option. High rates of discontinuation and therapy switching underscore the need for personalized treatment strategies and further evaluation of optimal sequencing in clinical practice."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

A Phase Ib Study of Novel Combination (New) of Low Dose Oral CyclophoSphamide (s) to Potentiate Axatilimab (A) + Retifanlimab (R) in Treating Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Phase classification: P1/2 ➔ P1 | Not yet recruiting ➔ Recruiting

Enrollment open • Phase classification • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Evaluation of health economic impacts of retifanlimab versus avelumab in patients with metastatic Merkel cell carcinoma in Germany: a cost-effectiveness analysis (DGHO 2025) - "Following international and German health economic guidelines, this study demonstrated cost-effectiveness of retifanlimab compared to avelumab."

Clinical • Cost effectiveness • HEOR • Metastases • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Redefining the Treatment of Squamous Cell Carcinoma of the Anal Canal (SCAC) | ZYNYZ® (retifanlimab-dlwr): The First and Only FDA-Approved PD-1 Inhibitor for Adults with Inoperable Locally Recurrent or Metastatic SCAC (SITC 2025) - "These studies offer important insights into the efficacy and safety profile of ZYNYZ in this rare and difficult-to-treat cancer. Join us to explore the evolving role of immunotherapy in SCAC and its potential impact on clinical practice."

Clinical • Metastases • Anal Carcinoma • Oncology • Squamous Cell Carcinoma

Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2). (clinicaltrials.gov) - P3 | N=308 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Sep 2025

Trial completion • Trial completion date • Anal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4

Addition of GITR Agonist to a Dark Matter Cancer Vaccine and anti-PD-1 Increases Regulatory T cell Numbers Without Appearing to Impact Therapeutic Efficacy (SITC 2025) - "Here we combined treatment groups for analysis of response to treatment and evaluated changes in PBMC.Methods Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) were randomized to receive a heterologous prime-boost regimen of DPV-001 with sequenced d.PD-1 (retifanlimab every 4 weeks), with or without a GITR agonist (INCAGN-1949 every 2 weeks). This occurred in the absence of a significant increase in the absolute numbers of CD3, CD4, or CD8 T cells.Conclusions DPV-001 in combination with delayed PD-1 blockade ± GITR agonist demonstrated promising clinical activity in HNSCC, with response rates of 56% in PD-1 naïve and 33% in PD-1 refractory patients. While not appearing to impact clinical efficacy of the treatment, the significant increase in peripheral blood Treg numbers in patients receiving GITR agonist underscores the complexities that need to be appreciated when developing combination immunotherapies."

Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

INCB161734-101: A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=710 | Recruiting | Sponsor: Incyte Corporation | N=466 ➔ 710

Enrollment change • Solid Tumor • KRAS

PRISM: Retifanlimab and Ruxolitinib In Solid Malignancies (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: University of California, San Diego

Checkpoint inhibition • New P1/2 trial • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

PRAC approved an extension of indication for Zynyz (retifanlimab) in combination with carboplatin and paclitaxel for adults with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC). The decision is supported by interim results from the Phase 3 INCMGA 0012-303 (POD1UM-303/InterAACT-2) study, with updates to SmPC sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 1 –4 Sep 2025

PRAC • Oncology • Squamous Cell Carcinoma of Head and Neck

Retifanlimab (Anti–PD-1 mAb) alone or in combination with Anti-LAG3 ± Anti-TIM3 mAbs In previously untreated, recurrent and/or metastatic (R/M) PD-L1+ HNSCC: A double-blind randomised controlled phase II trial (ESMO 2025) - P2 | "Methods Pts were randomised (1:1:1) to retifanlimab (RETI) alone, or RETI with tuparstobart (anti-LAG3 mAb; doublet tx) or RETI + tuparstobart and verzistobart (anti-TIM3 mAb; triplet tx). Conclusions This randomised phase 2 trial showed that adding anti-LAG3 ± anti-TIM3 did not significantly improve PFS vs RETI alone in pts with previously untreated R/M PD-L1+ HNSCC. Median PFS with RETI alone exceeded historical data from studies of other anti–PD-1 tx in R/M HNSCC."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Study to Evaluate INCB177054 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=9 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=322 ➔ 9

Enrollment change • Enrollment closed • Solid Tumor

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=83 | Terminated | Sponsor: Incyte Corporation | Active, not recruiting ➔ Terminated; The study was terminated after careful review of the overall clinical activity of this compound and a lack of robust efficacy. The study closure is not based on safety concerns.

Trial termination • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

Immune biomarkers of response in a phase 1 trial of combined MEK/STAT3/PD-1 inhibition in metastatic pancreatic ductal adenocarcinoma (PDAC) Free (AACRPanCa 2025) - P1 | "Based on these findings, we conducted a phase 1 trial (NCT05440942) to evaluate the safety, preliminary efficacy, and immune biomarkers of trametinib (MEKi), ruxolitinib (JAK/STAT3i), and retifanlimab (anti–PD-1) (TRRf), in patients with metastatic PDAC as second or third-line therapy. TRRf therapy was well tolerated in patients with metastatic PDAC and induced a distinct immune reprogramming in responders characterized by activation of memory/effector CD4+ T cells, innate cytotoxicity via NK cell expansion, and systemic Th1 cytokine induction. These circulating immune phenotypes and cytokine profiles may serve as predictive biomarkers and provide mechanistic insight into response to MEK/STAT3-targeted immunotherapy in PDAC."

Biomarker • IO biomarker • Metastases • P1 data • Anemia • Fatigue • Hematological Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD20 • CD4 • GZMB • IFNG • LAMP1 • STAT3

“Users of the Monitored Drug Registries are hereby informed that…it will be possible to use the medicinal product via the monitoring register for the indication eligible for reimbursement …ZYNYZ is indicated as monotherapy for the first-line treatment of adult patients with recurrent, locally advanced merkel cell carcinoma who are unresectable and unsuitable for radiotherapy.”[Google translation] (Italian Medicines Agency)

Reimbursement • Hematological Malignancies • Merkel Cell Carcinoma • Oncology

Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=61 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor • BRAF

9-ING-41 Combined With Retifanlimab, Plus Modified FOLFIRINOX for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Anwaar Saeed | Not yet recruiting ➔ Recruiting | Initiation date: May 2025 ➔ Sep 2025 | Trial primary completion date: May 2027 ➔ Sep 2027

Enrollment open • Trial initiation date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Retifanlimab versus placebo in combination with platinum-based chemotherapy in patients with first-line non-squamous or squamous metastatic non-small-cell lung cancer (POD1UM-304): a phase 3, multiregional, placebo-controlled, double-blind, randomised study. (PubMed, Lancet Respir Med) - P3 | "Retifanlimab improved overall survival compared with placebo when added to platinum-based chemotherapy, with a safety profile that is representative of previous PD-1 and PD-L1 inhibitor-chemotherapy combinations. Adding retifanlimab to first-line chemotherapy could be a potential treatment option for patients with squamous or non-squamous metastatic NSCLC."

IO biomarker • Journal • P3 data • Infectious Disease • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Solid Tumor