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

Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P2 | N=176 | Completed | Sponsor: Incyte Biosciences International Sàrl | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

PRISM: Phase 1b of Retifanlimab and Ruxolitinib In Solid Malignancies Progressing on Prior Checkpoint Inhibition (ESMO 2026) - No abstract available

Checkpoint inhibition • P1 data • Oncology • Solid Tumor

Final Survival Outcomes (OS) in POD1UM-303/InterAACT-2: a Phase 3 Study of Retifanlimab (R) + Carboplatin-Paclitaxel (CP) in First-Line (1L) Advanced Squamous Anal Cancer (SCAC) (ESMO 2026) - No abstract available

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

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

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 | Trial completion date: Dec 2028 ➔ Dec 2029 | Trial primary completion date: Sep 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Short-term Fasting Prior to PD-1/PD-L1 Inhibitor Therapy for of Advanced or Metastatic Skin Malignancy (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: University of Southern California | Trial completion date: Aug 2027 ➔ Mar 2028 | Trial primary completion date: Aug 2026 ➔ Mar 2027

Checkpoint inhibition • Trial completion date • Trial primary completion date • Oncology • Skin Cancer • Solid Tumor • LAG3

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. (PubMed, ESMO Open) - "The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches."

IO biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • HER-2 • MSI

Open-label, dose-escalation FIGHT-101 study of pemigatinib combined with targeted therapy, chemotherapy, or immunotherapy in patients with advanced malignancies. (PubMed, ESMO Open) - P1/2 | "Pemigatinib combination therapy showed no unexpected toxicities. PK and pharmacodynamics were mostly consistent with pemigatinib monotherapy. Pemi/gem/cis (37.5%) and pemi/pembro (26.9%) had the highest ORR; most responders had FGFR alterations."

IO biomarker • Journal • Metastases • 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

PD1 inhibition and GITR agonism in combination with fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma: A phase 2, multi-arm study. (ASCO 2023) - P2 | " This single-center trial enrolled patients with no prior bevacizumab and dexamethasone dose ≤ 2mg/day. The combination of retifanlimab, INCAGN01876, and FSRT did not demonstrate efficacy in patients with rGBM when administered without surgical resection. However, among patients receiving neoadjuvant immunotherapy prior to surgical resection, the addition of neoadjuvant FSRT was associated with a significant survival advantage as well as increased inflammatory and cellular immune responses. Neoadjuvant FSRT + ICB warrants further evaluation in rGBM."

Combination therapy • P2 data • Brain Cancer • CNS Disorders • CNS Tumor • Fatigue • Glioblastoma • Immune Modulation • Oncology • Solid Tumor

Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study. (PubMed, Lancet Oncol) - P2 | "Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies."

Journal • Metastases • P2 data • Acute Kidney Injury • Anal Carcinoma • Fatigue • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Nephrology • Neutropenia • Oncology • Renal Disease • Sarcoidosis • Solid Tumor • Squamous Cell Carcinoma • PD-1 • PD-L1

A phase II study of palbociclib combined with the PD-1 inhibitor retifanlimab in patients with advanced dedifferentiated liposarcoma (ESMO 2024) - P2 | "This study of P plus R has met its primary endpoint. A subset of pts have deep and durable responses. Correlative work is ongoing to identify biomarkers of response and resistance to this treatment combination."

Clinical • IO biomarker • Metastases • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

Neoadjuvant fractionated stereotactic radiotherapy with PD-1 blockade and GITR agonism is associated with prolonged survival and durable systemic immune activation in recurrent glioblastoma (EANO 2026) - "Cohort A (n=16) received retifanlimab (anti-PD-1), INCAGN01876 (anti-GITR agonist), and FSRT (8 Gy × 3 fractions) without surgical resection. Neoadjuvant FSRT combined with PD-1 blockade and GITR agonism followed by surgical resection was associated with improved OS and a distinct, durable pattern of systemic immune activation in rGBM, characterized by effector T cell expansion, sustained interferon signaling, and TCR repertoire diversification. These findings support a model of coordinated immuno-radiotherapy as an active immune-conditioning sequence in GBM."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • CXCL10 • CXCL11 • CXCL9

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

Retifanlimab Monotherapy as Neoadjuvant Therapy for Patients With Cisplatin (CDDP)-Ineligible Muscle-Invasive Urothelial Carcinoma of the Bladder (miUBC): Results From the Multicenter OPTIMUS Umbrella Study (IBCN 2024) - No abstract available

Clinical • Monotherapy • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma (clinicaltrials.gov) - P1/2 | N=98 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Preliminary immunological monitoring of first-in-human immunotherapy-trio for advanced head and neck squamous cell carcinoma (AACR 2022) - P1 | "Here we report preliminary immunological analyses of patients enrolled in a first-in-human immunotherapy-trio study of multivalent autophagosome vaccine (DPV-001), with sequenced checkpoint inhibition (anti-PD-1; retifanlimab), with/without anti-GITR agonist (INCAGN-1949), in recurrent or metastatic HNSCC (NCT04470024). Peripheral blood (PB) and sera are collected regularly and PB are evaluated by flow cytometry. We previously reported immunological monitoring of a phase I/II trial of an autophagosome cancer vaccine (DPV-001) containing more than 300 shared cancer antigens, as adjuvant therapy for NSCLC. Vaccination induced or augmented immune responses to more than 50 cancer antigens shared with head and neck squamous cell carcinoma (HNSCC). Preclinical studies combining this cancer vaccine with αGITR agonist and αPD-1 augmented therapeutic efficacy [PMID: 31747946], and provided the rationale for the current study."

P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

An off-the-shelf multivalent vaccine containing cancer's dark matter, DPV-001, combined with PD-1 +/- GITR in head & neck cancer: safety, efficacy, and immunodynamics from the phase 1 GITRVax trial (AACR 2024) - "Preclinical studies identified increased therapeutic efficacy when this vaccine strategy was combined with anti-PD-1 and anti-GITR, leading to this clinical trial for patients with advanced or metastatic HNSCC. Following safety run-in, eligible pts were randomly assigned 1:1 to receive DPV-001 +/- GITR agonist mAb (INCAGN-1949; q2wks). All received sequenced PD-1 mAb (retifanlimab; q4wks) starting D15... This 18 pt trial of DPV-001 and sequenced PD-1 +/- GITR shows a promising RR and evidence of increased activation and expansion of effector T cells in PBL and tumor. Upregulation of LAG-3 and TIM3 by T cells that infiltrate the tumor and have increased in number, provide a rationale for including inhibitors for both in this treatment strategy. Current efforts include evaluating whether immune responses target shared non-canonical alternative neoantigens, or Dark Matter, contained in DPV-001, and whether synchronized antibody and cellular response is evidenced."

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • GZMB • HAVCR2 • IFNG • LAG3 • PD-1

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

Update on anal dysplasia and anal cancer (PubMed, Dermatologie (Heidelb)) - "Therapeutically, destructive methods (such as electrocautery or trichloroacetic acid) and local immunomodulatory therapies (imiquimod) are used. Combining different therapeutic modalities is frequently a feasible strategy. For advanced anal cancer, recent studies such as POD1UM-303/InterAACT‑2 (immunotherapy with retifanlimab), as well as procedures like plasma HPV-ctDNA measurement (liquid biopsy) and dose-escalated/sparing radiation therapy, show promising results and give a perspective for the ongoing revision of the S3 guideline on anal cancer."

Journal • Review • Anal Carcinoma • Gynecologic Cancers • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer

Advanced Merkel cell carcinoma: High unmet medical need and clinical insights from the POD1UM-201 study of retifanlimab (ADO 2026) - "Sponsored by Incyte Biosciences Germany GmbH"

Clinical • Metastases • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. (PubMed, Front Oncol) - P3 | "The study is currently recruiting. https://clinicaltrials.gov/ct2/show/NCT04472429; https://clinicaltrialsregister.eu/ctr-search/search?query=2020-000826-24."

Clinical • IO biomarker • Journal • P3 data • Anal Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Human Immunodeficiency Virus • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Squamous Cell Carcinoma

Outcomes of advanced/metastatic breast cancer (aMBC) treated with BRIA-IMT, an allogeneic whole cell immunotherapy. (ASCO 2024) - P1/2, P3 | " Analysis of the phase 1 with expansion phase 2 cohort randomized by sequence using SV-BR-1-GM, checkpoint inhibitor (pembrolizumab or retifanlimab), low dose cyclophosphamide (Day –2) and post-dose local pegylated interferon α, with cycles every 3 weeks. BRIA-IMT has shown a favorable safety profile while providing benefits to heavily treated aMBC patients. Superior outcomes and survival were seen in patients treated with the phase III formulation and regimen now being used in the ongoing Ph3 trial, confirming the improvement in efficacy of the novel regimen. The results from this randomized phase 2 study informed the study design of the ongoing Ph3 trial comparing BRIA-IMT to standard of care physician choice treatments (NCT06072612)."

IO biomarker • Metastases • Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • CSF2 • CTCs • HER-2 • PGR

A PHASE II STUDY OF PALBOCICLIB COMBINED WITH THE PD-1 INHIBITOR RETIFANLIMAB IN PATIENTS WITH ADVANCED DEDIFFERENTIATED LIPOSARCOMA (CTOS 2024) - No abstract available

Clinical • Metastases • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo) (ESMO 2024) - P3 | "This international study demonstrates encouraging efficacy and favourable benefit/risk ratio for retifanlimab plus SoC chemo as first-line treatment of locally recurrent/metastatic SCAC and suggests a new SoC."

Clinical • Late-breaking abstract • Metastases • P3 data • Anal Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma