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

Comparison of T-cell activation status in patients treated with retifanlimab in combination with anti-LAG3/Anti-TIM3 vs retifanlimab alone (AACR 2026) - "INCAGN2385-203 is a randomized, phase 2 study to evaluate the efficacy and safety of retifanlimab (anti-PD-1) + INCAGN02385 (anti-LAG3) and retifanlimab + INCAGN02385 + INCAGN02390 (anti-TIM3) combinations vs retifanlimab alone in immunotherapy naïve PD-L1-positive (CPS ≥1) recurrent/metastatic SCCHN. LAG3 with PD-1 blockade may overstimulate T cells and lead to T-cell elimination, highlighting the need for dose optimization. Further evaluation of T-cell responses of PD-1/PD-L1 blockade with other checkpoint inhibitors, including those targeting LAG3 and TIM3, is warranted."

Clinical • Combination therapy • IO biomarker • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

Differential tumor and immune responses to anti PD-1 and DGK inhibition in patient-derived tumor spheroids reveal additive killing effect (AACR 2026) - "PDOTS from 22 patient tumors were treated with retifanlimab-dlwr (PD-1 inhibitor), DGK inhibitor (INC-DGKi) at two doses, or the combination...Combination therapy improved tumor killing but not immune engagement, suggesting complementarity of the two agents and merits additional studies to clarify the observed discordance between tumor regression and immune signals in the combination setting. These data support biomarker-guided approaches and highlight PDOTS as a translational platform for defining rational immunotherapy combinations."

Clinical • IO biomarker • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • DGKI • DGKZ

BRIA-ABC: Combination Study of SV-BR-1-GM With Retifanlimab (clinicaltrials.gov) - P1/2 | N=36 | Completed | Sponsor: BriaCell Therapeutics Corporation | Enrolling by invitation ➔ Completed | Trial completion date: Nov 2028 ➔ Mar 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • PGR • PIK3CA

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 | Trial completion date: Oct 2028 ➔ May 2026 | Trial primary completion date: Oct 2028 ➔ May 2026

Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • PD-L1

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

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

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 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

ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1 (clinicaltrials.gov) - P1/2 | N=31 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

New P1/2 trial • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Retifanlimab With or Without Difluoromethylornithine for the Treatment of Progressive High Grade Gliomas (clinicaltrials.gov) - P1/2 | N=33 | Not yet recruiting | Sponsor: Mayo Clinic

New P1/2 trial • Anaplastic Astrocytoma • Anaplastic Oligoastrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2

Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2030 ➔ Mar 2029 | Trial primary completion date: Apr 2027 ➔ Apr 2026

Enrollment closed • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

On February 27, 2026, the U.S. Food and Drug Administration ('FDA') issued a Complete Response Letter ('CRL') for the supplemental Biologics License Application ('sBLA') for Zynyz (retifanlimab-dlwr) injection (375mg) for an additional indication for the treatment of adult patients with metastatic non-small cell lung cancer ('NSCLC') in combination with platinum-bas (Incyte) - "The sBLA was supported by positive efficacy and safety data from the Phase 3 POD1UM-304 trial announced in December 2024. The CRL cited inspection findings (not specific to Zynyz) at Catalent Indiana, LLC ('Catalent Indiana'), part of Novo Nordisk....The CRL cited the regulatory compliance of Catalent Indiana as the sole approvability issue, and did not cite other approvability concerns, including Zynyz’s efficacy and safety data in NSCLC or the third-party drug substance manufacturer. Incyte Corporation is working closely with the FDA and Catalent Indiana to address the CRL and support a potential sBLA resubmission of Zynyz in NSCLC."

CRL • Non Small Cell Lung Cancer

Incyte…announced that the European Commission (EC) has approved Zynyz (retifanlimab) in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with metastatic or with inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC) (Businesswire) - "The EC decision follows the January 2026 positive opinion received from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP)....This approval is based on data from the Phase 3 POD1UM-303/InterAACT2 trial (NCT04472429) evaluating Zynyz or placebo in combination with platinum-based chemotherapy (carboplatin and paclitaxel) in adult patients with metastatic or inoperable locally recurrent SCAC not previously treated with systemic chemotherapy."

EMA approval • Anal Squamous Cell Carcinoma

Dr Kim on Upfront vs Second-Line Use of Retifanlimab in Metastatic SCAC (OncLive) - "Ultimately, although certain conditions such as autoimmune disease represent a relative contraindication, Kim concluded that for most patients with advanced SCAC, there is no clinical reason to withhold frontline immunotherapy. These findings reinforce the value of incorporating retifanlimab into the standard of care to optimize long-term patient outcomes, Kim concluded."

Video

Retifanlimab Combination Signals a New Era of Chemoimmunotherapy in Frontline Advanced Anal Cancer (OncLive) - "'Based on this positive phase 3 study, if I see a patient in my clinic with advanced anal cancer, irrespective of any biomarkers currently out there - because we don't have many - I would choose carboplatin and paclitaxel plus retifanlimab in the first-line setting,' Kim shared in an interview with OncLive. 'This ensures that the patient is exposed to immunotherapy earlier on, which is something patients want. Hopefully, we can improve overall survival [OS] as well.'"

Audio • Interview

HPV ctDNA Response-Adapted Chemoradiation +/- Retifanlimab Treatment in Advanced-Stage Anal Cancer (clinicaltrials.gov) - P2 | N=33 | Not yet recruiting | Sponsor: Jennifer Dorth

Circulating tumor DNA • New P2 trial • Anal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4 • DPYD • IFNG

Total net product revenue for the quarter and year ended December 31, 2025 increased 20% over the prior year comparative periods, primarily driven by the following (Businesswire) - "Niktimvo net product revenue increased 22% versus the third quarter of 2025 to $56 million driven by strong uptake following the product launch in the first quarter of 2025...For the quarter and year ended December 31, 2025, Monjuvi/Minjuvi net product revenue increased 28% to $42 million and 21% to $145 million, respectively, driven by the approval and launch in r/r FL; For the quarter and year ended December 31, 2025, Zynyz net product revenue was $32 million and $66 million, respectively, with growth driven by the approval and launch in SCAC."

Sales • Anal Squamous Cell Carcinoma • Chronic Graft versus Host Disease • Follicular Lymphoma

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

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

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

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

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

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

Efficacy and safety of checkpoint inhibitors combined with chemotherapy in advanced endometrial cancer: a systematic review and meta-analysis (ESGO 2026) - "Results Five RCTs met inclusion criteria (NRG-GY018 [pembrolizumab+carboplatin-paclitaxel, n=816], RUBY [dostarlimab+carboplatin-paclitaxel, n=690], AtTEnd [atezolizumab+carboplatin-paclitaxel, n=550], POD1UM-204 [retifanlimab+chemotherapy, n=412], DUO-E [durvalumab+carboplatin-paclitaxel, n=718]; total n=3,186, mean age 63 years, 66% proficient mismatch repair [pMMR]). Results advocate for routine MMR/MSI testing and ICI integration into first-line therapy, aligning with 2025 ESGO/NCCN guidelines. Future research should optimise pMMR outcomes through novel combinations."

Checkpoint inhibition • Metastases • Retrospective data • Review • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • PD-1