ragifilimab (INCAGN1876) / Agenus, Incyte - LARVOL DELTA

Anti-GITR/Anti-PD1/Stereotactic Radiosurgery, in Recurrent Glioblastoma (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jun 2025 ➔ Apr 2029

Trial completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT • TERT

First-in-Human Phase 1/2 Study of INCAGN01876, a Glucocorticoid-Induced Tumor Necrosis Factor Receptor Agonist, in Patients with Advanced or Metastatic Solid Tumors. (PubMed, Clin Cancer Res) - P1/2 | "INCAGN01876 was generally well tolerated; fatigue was the most frequent TRAE. INCAGN01876 elicited transient and variable Treg depletion and limited antitumor activity. Future studies will explore combinatorial approaches."

IO biomarker • Journal • P1/2 data • Appendix Cancer • Colorectal Cancer • Dermatology • Fatigue • Melanoma • Mucinous carcinoma • Oncology • Pruritus • Respiratory Diseases • Solid Tumor • TNFA

Dr Leidner on the Multivalent Vaccine DPV-001 in Advanced or Metastatic HNSCC (OncLive) - P1 | N=56 | NCT04470024 | "In the study, 18 patients received DPV-001 with sequenced a novel PD-1 therapy, INCMGA00012. Nine of these patients also received the GITR agonist INCAGN01876 starting on day 1....Leidner notes that the overall response rate (ORR) for patients with PD-1–naive disease was 55.5% (n = 5/9), and the ORR was 33.3% (n = 3/9) for patients previously treated with PD-1 therapy patients."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Providence Health & Services | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2024 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Checkpoint inhibition • Enrollment open • Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

UPSTREAM: Biomarker-based Study in R/M SCCHN (clinicaltrials.gov) - P2 | N=340 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • IO biomarker • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Multi-parametric assessment of the immune response to a trio immunotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (SITC 2023) - P1 | "Methods Patients received DPV-001, with sequenced checkpoint inhibition (aPD-1 mAb; retifanlimab), with or without aGITR agonist mAb (INCAGN1876), in recurrent or metastatic HNSCC (NCT04470024). Increased expression of LAG3 by T cells that infiltrate and have expanded in the tumor, provide a rationale for including anti-LAG-3 in this treatment strategy. Future plans include evaluating whether immune responses target shared non-canonical alternative neoantigens, or Dark Matter, contained in DPV-001 and whether antibody responses identify targets of cellular immunity."

Clinical • IO biomarker • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ENTPD1 • GZMB • IFNG • ITGAE

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Providence Health & Services | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

Combining GITR inhibitors with immunotherapy in advanced cancers (YouTube) - "Omid Hamid, MD...provides an overview of a Phase I/II trial (NCT03126110) of INCAGN01876, a GITR inhibitor, with PD-1 and CTLA-4 inhibitors in patients with advanced cancers. Preliminary efficacy was observed in patients and no novel toxicities and adverse events were seen. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL."

Interview • Video

A phase 1/2 study of the safety, tolerability, and preliminary efficacy of the anti-GITR monoclonal antibody, INCAGN01876, combined with immunotherapies (IO) in patients (Pts) with advanced cancers. (ASCO 2023) - P1/2 | " This global open-label nonrandomized phase 1/2 study assessed the safety, tolerability, recommended phase 2 dose (RP2D), and efficacy of INCAGN01876 + nivolumab (NIVO) and/or ipilimumab (IPI) (NCT03126110). INCAGN01876 plus NIVO and/or IPI was generally well tolerated in pts with advanced tumors; most common toxicities were mild to moderate pruritus and rash. No novel safety signals were seen. INCAGN01876 300 mg Q2W was selected as RP2D based on safety and preliminary PK/PD data and used for expansion in combination with NIVO or IPI."

Clinical • Metastases • P1/2 data • Anemia • Breast Cancer • Cervical Cancer • Dermatology • Hematological Disorders • Infectious Disease • Kidney Cancer • Lung Cancer • Oncology • Ovarian Cancer • Pneumonia • Pruritus • Renal Cell Carcinoma • Respiratory Diseases • 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

INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Incyte Biosciences International Sàrl | N=47 ➔ 0 | Recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Metastases • Trial withdrawal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Trial in progress: First-in-human immunotherapy-trio for advanced head and neck squamous cell carcinoma (AACR 2023) - P1 | "We hypothesize that addition of aGITR to DPV-001 vaccine will augment expansion of reactive CD4 and CD8 T cells, attenuate contraction of this response, and improve the therapeutic effect of treatment, and will result in the development of a coordinated T and B cell response to some of the same proteins, detectable using a cutting-edge seromics approach, as a window to TCR target identification for immunodynamic tracking of induced anti-cancer responses at an advanced level. Patient recruitment began in August 2022, for this first-in-human immunotherapy-trio study of DPV-001, with sequenced checkpoint inhibition (aPD-1 mAb; retifanlimab), with or without aGITR agonist mAb (INCAGN-1949), in recurrent or metastatic HNSCC (NCT04470024)...Initial safety lead-in (n = 3+3 per arm), will be followed by phase Ib expansion of one/both arms if immunologically promising, 28 patients per arm, futility if <4/15 responses.Study DrugsCyclophosphamide 300mg/m2 IV, priming Day..."

Metastases • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • TNFA

A phase II study of GITR agonist INCAGN01876 and PD-1 inhibitor retifanlimab in combination with stereotactic radiotherapy in patients with recurrent glioblastoma (SNO 2022) - "The combination of retifanlimab, INCAGN01876, and FSRT is generally well-tolerated in patients with recurrent GBM when administered with or without surgical resection. Survival outcomes in the neoadjuvant cohort are encouraging, largely driven by patients that received neoadjuvant FSRT."

Clinical • Combination therapy • P2 data • Brain Cancer • CNS Disorders • Cognitive Disorders • Glioblastoma • Oncology • Solid Tumor • MGMT

INCAGN1876, a unique GITR agonist antibody that facilitates GITR oligomerization (AACR 2017) - P1/2; "The superiority of an IgG1 antibody in these assays was consistent with the potential to achieve optimal GITR clustering by FcγRs, while maintaining the potential for FcγR-mediated effector cell activity directed toward intratumoral GITRhigh regulatory T cells. INCAGN1876 is currently under evaluation in Phase 1/2 studies in subjects with advanced metastatic solid tumors (NCT02697591)."

Biomarker • Clinical • Biosimilar • Immune Modulation • Inflammation • Oncology

A phase 2, open-label, multicenter study of INCAGN01876 (anti-GITR agonist) in combination with retifanlimab (anti-PD-1) in recurrent or metastatic head and neck squamous cell carcinoma (SITC 2022) - P2 | "Trial Registration Clinicaltrials. gov identifier NCT05359692 Ethics Approval The study protocol was approved by institutional review boards or independent ethics committees at participating centers."

Clinical • Combination therapy • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TNFA

Data From Incyte’s Oncology Portfolio to Be Presented at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting (Businesswire) - "Incyte...will be presented at the upcoming Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting, held November 8-12, 2022, in Boston and virtually....'We look forward to presenting data at the SITC Annual Meeting from our immuno-oncology pipeline, including our oral PD-L1 program, as we make progress toward our goal of identifying new solutions for patients with cancer who need additional options'."

P1 data • P2 data • Cervical Cancer • Cutaneous Melanoma • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Nasopharyngeal Carcinoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Urothelial Cancer

INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=47 | Recruiting | Sponsor: Incyte Biosciences International Sàrl | Trial completion date: Jun 2024 ➔ Dec 2024

Combination therapy • Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=47 | Recruiting | Sponsor: Incyte Biosciences International Sàrl | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Jun 2024

Combination therapy • Enrollment open • Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Incyte Biosciences International Sàrl

Combination therapy • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Anti-GITR/Anti-PD1/Stereotactic Radiosurgery, in Recurrent Glioblastoma (clinicaltrials.gov) - P2 | N=32 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT • TERT

UbiVac Announces Preliminary Immunological Data from 1st-In-Human Trial of DPV-001 Immunotherapy Trio for Advanced HNSCC (EIN News) - "Data from Clinical Trial of DPV-001 & Anti-PD-1 +/- anti-GITR for Head & Neck Squamous Cell Cancer (HNSCC) Presented at American Association for Cancer Research."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1/2 | N=145 | Completed | Sponsor: Incyte Biosciences International Sàrl | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-1 • PD-L1

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1/2; N=145; Active, not recruiting; Sponsor: Incyte Biosciences International Sàrl; Trial completion date: Sep 2021 ➔ Jan 2022

Clinical • Combination therapy • Trial completion date • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-1 • PD-L1

UPSTREAM: Biomarker-based Study in R/M SCCHN (clinicaltrials.gov) - P2; N=340; Recruiting; Sponsor: European Organisation for Research and Treatment of Cancer - EORTC; Trial completion date: Dec 2021 ➔ Dec 2025; Trial primary completion date: Jun 2021 ➔ Jun 2025

Biomarker • Clinical • IO biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MRI

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Providence Health & Services; Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4