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

Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial. (PubMed, Lancet) - P3 | "Retifanlimab provides clinical benefit, with a manageable safety profile, when added to first-line chemotherapy in advanced squamous cell carcinoma of the anal canal. These results suggest retifanlimab with carboplatin plus paclitaxel should be considered as the new standard of care for patients with advanced squamous cell anal carcinoma."

Clinical • Journal • P3 data • Anal Carcinoma • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Neutropenia • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4 • PD-L1

Study of 225Ac-SS0110 in Subjects With ES-SCLC or MCC (SANTANA-225 ) (clinicaltrials.gov) - P1/2 | N=2 | Terminated | Sponsor: Ariceum Therapeutics GmbH | N=50 ➔ 2 | Trial completion date: Dec 2026 ➔ Dec 2025 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2026 ➔ Dec 2025; Study terminated due to strategic business decisions.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

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

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

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

IRENE study: Phase 2 study of oncolytic virus pelareorep and PD-1 inhibitor retifanlimab in metastatic triple negative breast cancer (SABCS 2024) - P2 | "Five patients received prior treatment with checkpoint inhibitors - pembrolizumab or atezolizumab. One patient had a partial response. Tumor tissue, stool and blood samples collected during treatment will be assessed to understand the role of PD-L1 expression and gut microbiome, especially in the patient with response."

IO biomarker • Metastases • Oncolytic virus • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

Zynyz - opinion on variation to marketing authorisation (European Medicines Agency) - "On 29 January 2026, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Zynyz....Zynyz is indicated in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with metastatic or with inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC)."

CHMP • Anal Squamous Cell Carcinoma

All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma (clinicaltrials.gov) - P2 | N=55 | Recruiting | Sponsor: Stephen Bagley, MD, MSCE | Trial completion date: Jun 2027 ➔ Jun 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2027

IO biomarker • Trial completion date • Trial primary completion date • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

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

Avelumab real-world use in advanced Merkel cell carcinoma: a systematic review and non-comparative meta-analysis. (PubMed, Future Oncol) - "Programmed death (ligand) 1 inhibitors (e.g., avelumab, pembrolizumab, and retifanlimab) are first-line treatment options for patients with locally advanced or metastatic Merkel cell carcinoma (MCC). Although safety data were insufficient for meta-analysis, two retrospective studies reported lower adverse event rates than JAVELIN Merkel 200. The results of this study support broader use of avelumab in advanced MCC."

Journal • Real-world evidence • Retrospective data • Review • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

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

Overall Survival Results of Bria-IMT Allogenic Whole Cell-Based Cancer Vaccine. (SABCS 2024) - P1/2, P3 | "Methods This phase I/II study evaluated the Bria-IMT regimen consisting of low-dose cyclophosphamide (Day –2) followed by SV-BR-1-GM and CPI (pembrolizumab or retifanlimab), then low-dose local peg- interferon α, all given every 3 wks. In heavily pretreated MBC patients, the Bria-IMT regimen demonstrated promising results across all subtypes of breast cancer with favorable safety profiles. There was no significant difference in OS among patients treated with immediate vs. delayed CPI."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Triple Negative Breast Cancer • CSF2 • CTCs • HER-2 • IFNG • PD-L1 • PGR

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

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

Phase II study of the efficacy of retifanlimab (Rf) (INCMGA00012) in penile squamous cell carcinoma (PSqCC): ORPHEUS final analysis. (ASCO 2023) - P2 | "Rf in monotherapy showed signals of clinical activity in advanced or metastatic PSqCC pts. Safety profile was consistent with previous data. These results along with identification of suitable biomarkers could help to develop novel immunotherapy combination strategies in this orphan genitourinary tumor."

Clinical • IO biomarker • P2 data • Anemia • Dermatology • Fatigue • Infectious Disease • Oncology • Penile Cancer • Skin Cancer • Squamous Cell Carcinoma • PD-L1

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 in Advanced Penile Squamous Cell Carcinoma: The Phase 2 ORPHEUS Study. (PubMed, Eur Urol Oncol) - "Single-agent retifanlimab exhibited signals of clinical activity in advanced/metastatic PSCC, with no new safety signals. Further investigation of retifanlimab in this setting is warranted."

IO biomarker • Journal • Metastases • P2 data • Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma

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

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

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