izuralimab (XmAb23104) / Xencor - LARVOL DELTA

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy (clinicaltrials.gov) - P1 | N=6 | Terminated | Sponsor: University of California, San Francisco | Trial completion date: Dec 2025 ➔ Apr 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Apr 2024; Sponsor decision

Checkpoint inhibition • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Melanoma • Oncology • Solid Tumor • BRAF • LAG3 • PD-L1

A Study of XmAb23104 in People With Sarcoma (clinicaltrials.gov) - P2 | N=6 | Terminated | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2025 ➔ Jul 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Apr 2025 ➔ Jul 2024; Vendor decided study to be closed early

Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Sarcoma • Solid Tumor

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1 | N=198 | Completed | Sponsor: Xencor, Inc. | Active, not recruiting ➔ Completed | N=300 ➔ 198 | Trial completion date: Sep 2025 ➔ Feb 2024 | Trial primary completion date: Dec 2024 ➔ Feb 2024

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: University of California, San Francisco | Recruiting ➔ Active, not recruiting | Phase classification: P1/2 ➔ P1 | N=46 ➔ 6

Checkpoint inhibition • Enrollment change • Enrollment closed • Metastases • Phase classification • CNS Disorders • Melanoma • Oncology • Solid Tumor • BRAF • LAG3 • PD-L1

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1 | N=300 | Active, not recruiting | Sponsor: Xencor, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

A Study of XmAb23104 in People With Sarcoma (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting | N=30 ➔ 6 | Trial completion date: Apr 2028 ➔ Apr 2025 | Trial primary completion date: Apr 2028 ➔ Apr 2025

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Phase Ib/II Study of XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) combination in metastatic melanoma refractory to prior immune checkpoint Inhibitor therapy with and without CNS disease (SITC 2023) - P1/2 | "1. At the time of this abstract submission, Cohort 1 of dose escalation has begun with the first few patients still within the DLT observation window."

Checkpoint inhibition • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor • CTLA4 • ICOS • LAG3 • PD-1

Xencor Reports Third Quarter 2023 Financial Results (Businesswire) - "Pipeline Updates:...XmAb104 (PD-1 x ICOS): Xencor will stop internal development of XmAb104 due to emerging data from Phase 1 expansion cohorts not meeting efficacy criteria for advancing the program. The study expansion enrolled patients with microsatellite stable colorectal cancer with or without liver metastases. The Company will continue to support patients currently enrolled and being treated."

Discontinued • Colorectal Cancer

Phase Ib/II study of XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) combination in metastatic melanoma refractory to prior immune checkpoint inhibitor therapy with and without CNS disease. (ASCO 2023) - P1, P1/2 | "At the time of this abstract submission, Cohort 1 of dose escalation has begun with the first few patients still within the DLT observation window. Clinical trial information: NCT05695898."

Checkpoint inhibition • Metastases • P1/2 data • CNS Disorders • Immune Modulation • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • CTLA4 • ICOS • LAG3 • PD-1

A Study of XmAb23104 in People With Sarcoma (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Metastases • New P2 trial • Oncology • Sarcoma • Solid Tumor

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: Xencor, Inc. | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Jul 2023 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy (clinicaltrials.gov) - P1/2 | N=46 | Recruiting | Sponsor: University of California, San Francisco | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Metastases • CNS Disorders • Immune Modulation • Melanoma • Oncology • Solid Tumor • BRAF • LAG3 • PD-L1

XmAb23104 (PD1 X ICOS) and XmAb22841 (CTLA-4 X LAG3) in Treating Melanoma Prior Immune Checkpoint Inhibitor Therapy (clinicaltrials.gov) - P1/2 | N=46 | Not yet recruiting | Sponsor: University of California, San Francisco

Checkpoint inhibition • Metastases • New P1/2 trial • CNS Disorders • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • BRAF • LAG3 • PD-L1

Xencor Highlights 2023 Corporate Priorities and Provides Portfolio Updates (Businesswire) - "Plamotamab: Xencor plans to...Continue enrolling patients into the Phase 1 subcutaneous dose escalation study; Vudalima: Xencor plans to...Continue enrolling patients into the two Phase 2 clinical studies of vudalimab; XmAb104: Xencor plans to: Continue enrolling patients into the expansion portion of the Phase 1 clinical study; XmAb819: . Xencor plans to...Continue enrolling patients into the Phase 1 dose-escalation study in patients with RCC."

Enrollment status • Genito-urinary Cancer • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

A phase 1 multiple-ascending dose study to evaluate the safety and tolerability of XmAb23104 (PD-1 x ICOS) in subjects with selected advanced solid tumors (DUET-3). (ASCO 2022) - P1 | "A minimum 6-week washout from prior pembrolizumab was required. The dose escalation part of this study indicates XmAb23104 was generally well tolerated at doses up to 15 mg/kg and has shown clinical activity in subjects with advanced solid tumors. CTLA4 blockade has been found to increase the frequency of ICOS-expressing T cells in prostate cancer, bladder cancer, melanoma, and hepatocellular cancer (Chen, 2009; Liakou, 2008; Wei, 2017) and may be applicable to other immunogenic tumor types. XmAb23104 is currently being studied alone or in combination with ipilimumab in expansion in non-squamous non-small cell lung carcinoma, melanoma, CRC, undifferentiated pleomorphic sarcoma, HNSCC, and RCC."

Clinical • P1 data • Bladder Cancer • Colorectal Cancer • Dermatology • Fatigue • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Immune Modulation • Inflammation • Liver Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Pruritus • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • ICOS • MSI • PD-1

"The sun sets on #Icos (via @JacobPlieth) https://t.co/w4C44YkWk5 #vopratelimab #Izuralimab $JNCE $XNCR $AZN $BMY $GSK" (@evaluatevantage)

ICOS

Xencor Reports Initial Dose-Escalation Data from Phase 1 Study of XmAb104, PD-1 x ICOS Bispecific Antibody, in Advanced Solid Tumors (Businesswire) - P1 | N=234 | DUET-3 (NCT03752398) | Sponsor: Xencor, Inc | "At the data cut off on April 15, 2022, 62 patients had been treated in nine dose-escalation cohorts escalating from 0.002 to 15 mg/kg of XmAb104 administered every other week in four-week cycles. Patients were a median age of 63 years and had a median of three prior systemic therapies. 62.9% of patients had received at least one prior checkpoint therapy, and 91.9% of patients had Stage IV disease. Patients presented with the following primary tumor types: CRC (n=14), pancreatic adenocarcinoma (n=8), soft tissue sarcoma (n=8), melanoma (n=6), HNSCC (n=5), RCC (n=4), endometrial cancer (n=2), NSCLC (n=2) and other solid tumor types (n=8). Of the patients with CRC, eight were microsatellite stable (MSS), three were microsatellite instable (MSI) and three were not defined. Most patients had tumors generally not considered to be sensitive to checkpoint inhibition."

P1 data • Oncology

Xencor Reports First Quarter 2022 Financial Results (Businesswire) - "An abstract with initial dose-escalation data from the Phase 1 study of XmAb104 in patients with advanced solid tumors was accepted for a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2022."

P1 data • Oncology • Solid Tumor

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1; N=234; Recruiting; Sponsor: Xencor, Inc.; Trial completion date: Mar 2025 ➔ Dec 2024; Trial primary completion date: Sep 2024 ➔ Jul 2023

Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Undifferentiated Pleomorphic Sarcoma • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1; N=234; Recruiting; Sponsor: Xencor, Inc.; N=164 ➔ 234

Clinical • Enrollment change • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1; N=144; Not yet recruiting; Sponsor: Xencor, Inc.

Clinical • New P1 trial • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3) (clinicaltrials.gov) - P1; N=144; Recruiting; Sponsor: Xencor, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Urothelial Cancer • Uveal Melanoma • ER • HER-2 • PGR

Xencor and MD Anderson Enter Strategic Collaboration to Advance Investigational XmAb Drug Candidates (Businesswire) - "Xencor, Inc…and The University of Texas MD Anderson Cancer Center today announced a strategic collaboration to study investigational treatments for patients with a variety of cancer types. The parties will collaborate to design and execute additional clinical studies with Xencor’s portfolio of XmAb® drug candidates, including novel bispecific antibodies and engineered cytokines. Xencor is committing to funding and supporting these studies over an initial five-year term."

Licensing / partnership • Oncology

Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation (AACR 2018) - "We developed optimized bispecific antibody candidates that simultaneously engage PD1 and CTLA4 (XmAb20717), CTLA4 and LAG3 (XmAb22841), and PD1 and ICOS (XmAb23104), that preferentially bind to cells co-expressing the targeted receptors. Each bispecific antibody promoted a unique RNA gene signature suggesting distinct mechanisms of action. These bispecific antibodies demonstrate compelling immune modulatory activity suggesting clinical development is warranted for the treatment of human malignancies."

IO Biomarker • PD(L)-1 Biomarker • Oncology

Xencor doses first patient in phase 1 study of XmAb23104 for the treatment of patients with advanced solid tumors (Businesswire) - “Xencor, Inc….announced that the first patient has been dosed in XmAb23104-01 (DUET-3), a Phase 1 clinical study to evaluate the safety and tolerability of XmAb23104, a bispecific antibody that simultaneously targets the immune receptors PD-1 and ICOS, for the treatment of patients with advanced solid tumors.”

Enrollment open