vudalimab (XmAb717) / Xencor - LARVOL DELTA

Vudalimab for the Treatment of Locally Advanced or Metastatic Anaplastic Thyroid Cancer or Hurthle Cell Thyroid Cancer (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: Northwestern University | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Jul 2027 | Trial primary completion date: Jul 2024 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Oncocytic Carcinoma • BRAF • CD4

Vudalimab (XmAb20717) in Combination With Standard of Care Treatment in Patients With Metastatic Castration Sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Emory University | N=30 ➔ 4 | Trial completion date: Dec 2027 ➔ Jun 2025 | Suspended ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Jun 2025; To review the safety data.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

XmAb20717-04: XmAb®20717 (Vudalimab) Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=72 | Completed | Sponsor: Xencor, Inc. | Active, not recruiting ➔ Completed

Trial completion • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD • MSI • TMB

XmAb20717-04: XmAb®20717 (Vudalimab) Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: Xencor, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Jun 2025

Enrollment closed • Trial completion date • Tumor mutational burden • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD • MSI • TMB

A Phase II Clinical Trial to Evaluate Safety and Efficacy of XmAb20717 in Advanced Rare Cancers (clinicaltrials.gov) - P2 | N=140 | Suspended | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Cervical Cancer • Classical Hodgkin Lymphoma • Endocrine Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Peritoneal Mesothelioma • Pleural Mesothelioma • Small Cell Lung Cancer • Solid Tumor • MSI

Clinical Program Updates and 2025 Priorities (Businesswire) - "Vudalimab (PD-1 x CTLA-4), a bispecific antibody that targets two immune checkpoint receptors for selective activation of T cells. In the fourth quarter of 2024, we completed enrollment in two studies of vudalimab in patients with metastatic castration-resistant prostate cancer (mCRPC) and in Part 1 of a study in patients with locally advanced or metastatic non-small cell lung cancer. Xencor has paused further development of vudalimab and has prioritized resources to advance other pipeline programs. Safety data from the three studies of vudalimab remain consistent with prior data disclosures."

Discontinued • Enrollment closed • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

XmAb20717-05: A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies (clinicaltrials.gov) - P2 | N=170 | Active, not recruiting | Sponsor: Xencor, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Cervical Cancer • Clear Cell Carcinoma • Endometrial Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Prostate Cancer • Solid Tumor

CS2009, a novel first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFa, demonstrates promising anti-tumor activity in preclinical evaluation (SITC 2024) - "One strategy to overcome this problem is to build bispecific molecules aiming to 1) attenuate anti-CTLA-4 arm to balance the immune-toxicity and immune-efficacy (e.g. cadonilimab and KN046); 2) preferentially bind to PD-1/CTLA-4 double positive tumor infiltrating T cells (TILs) (e.g. volrustomig and vudalimab). To improve the effect of ICB, VEGF inhibitors including bevacizumab, ramucirumab, lenvatinib, etc. were applied to interrupt tumor angiogenesis, hence promote vascular normalization in tumor immune microenvironment, and improve T lymphocyte infiltration...In the studies using immune competent humanized mice, J30 showed superior anti-tumor activities to its major competitors such as cadonilimab, AK112 and volrustomig...Conclusions J30 is a promising trispecific molecule for the treatment of various advanced solid tumors as a next-generation ICB. Current data supports further clinical research on CS2009."

IO biomarker • Preclinical • Trispecific • Oncology • Solid Tumor

CS2009, a novel first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFa, demonstrates promising anti-tumor activity in preclinical evaluation (SITC 2024) - "One strategy to overcome this problem is to build bispecific molecules aiming to 1) attenuate anti-CTLA-4 arm to balance the immune-toxicity and immune-efficacy (e.g. cadonilimab and KN046); 2) preferentially bind to PD-1/CTLA-4 double positive tumor infiltrating T cells (TILs) (e.g. volrustomig and vudalimab). To improve the effect of ICB, VEGF inhibitors including bevacizumab, ramucirumab, lenvatinib, etc. were applied to interrupt tumor angiogenesis, hence promote vascular normalization in tumor immune microenvironment, and improve T lymphocyte infiltration...In the studies using immune competent humanized mice, J30 showed superior anti-tumor activities to its major competitors such as cadonilimab, AK112 and volrustomig...Conclusions J30 is a promising trispecific molecule for the treatment of various advanced solid tumors as a next-generation ICB. Current data supports further clinical research on CS2009."

IO biomarker • Preclinical • Trispecific • Oncology • Solid Tumor

XmAb20717 in Advanced Biliary Tract Cancers (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NTRK

Vudalimab (XmAb20717) in Combination With Standard of Care Treatment in Patients With Metastatic Castration Sensitive Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Suspended | Sponsor: Emory University | Recruiting ➔ Suspended

Trial suspension • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

XmAb20717-05: A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: Xencor, Inc. | Trial completion date: May 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Oct 2025

Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Endometrial Cancer • Genito-urinary Cancer • Gynecologic Cancers • Metastatic Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Prostate Cancer • Solid Tumor

Xencor Reports Second Quarter 2024 Financial Results (Businesswire) - "Bispecific Antibody Programs Advancing in Internal Clinical Development:...Vudalimab, a selective dual checkpoint inhibitor of PD-1 and CTLA-4, is advancing in multiple clinical studies, including a monotherapy study in patients with clinically defined high-risk metastatic castration-resistant prostate cancer (mCRPC; Study XmAb717-05), a study in combination with docetaxel in patients with mCRPC (Study XmAb717-04), and a study in combination with chemotherapy in patients with non-small cell lung cancer (Study XmAb717-06). Xencor continues to anticipate a data update and decision whether to advance vudalimab for patients with mCRPC in the first half of 2025."

P2 data • Trial status • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

A Phase II Clinical Trial to Evaluate Safety and Efficacy of XmAb20717 in Advanced Rare Cancers (clinicaltrials.gov) - P2 | N=140 | Suspended | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Suspended

Metastases • Trial suspension • Cervical Cancer • Endocrine Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • MSI

XmAb20717 in Advanced Biliary Tract Cancers (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Trial primary completion date: Mar 2024 ➔ Dec 2024

Metastases • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NTRK

XmAb®20717 (Vudalimab) Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=85 | Recruiting | Sponsor: Xencor, Inc. | Trial completion date: Jun 2024 ➔ Sep 2025 | Trial primary completion date: Jun 2023 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Tumor mutational burden • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD • MSI • TMB

Xencor Reports Fourth Quarter and Full Year 2023 Financial Results (Businesswire) - P2 | N=150 | NCT05032040 | Sponsor: Xencor, Inc. | "Xencor is advancing vudalimab...in multiple clinical studies, including a Phase 2 monotherapy study (Study XmAb717-05) in patients with clinically defined high-risk...mCRPC....At the February 7, 2024 data cut off, 14 patients with clinically defined high-risk mCRPC had been treated with vudalimab every three weeks at a flat dose of 1000 mg, or 1200 mg for patients greater than 80 kg....The efficacy-evaluable population included 12 patients who had baseline and at least one post-baseline RECIST assessment. The objective response rate was 33% (4/12). Three patients had a confirmed partial response per RECIST 1.1 guidelines, and one additional patient had an unconfirmed partial response. An additional two patients experienced a best overall response of stable disease. Prostate-specific antigen (PSA) reductions of more than 90% from baseline (PSA90) were observed in 25% (3/12) of evaluable patients."

P2 data • Metastatic Castration-Resistant Prostate Cancer

Xencor Reports Fourth Quarter and Full Year 2023 Financial Results (Businesswire) - "In the fourth quarter of 2023, the Company dosed the first patient in a Phase 1b/2 study (Study XmAb717-06) evaluating vudalimab as a first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Xencor plans to: (i) Continue enrollment and provide a data update and decision whether to advance vudalimab as a monotherapy for patients with mCRPC in the first half of 2025; (ii) Continue enrollment and provide a data update and decision whether to advance vudalimab in combination with chemotherapy for patients with mCRPC in the first half of 2025; (iii) Continue to enroll the Phase 1b part of a study of vudalimab in front-line metastatic NSCLC."

Clinical • P2 data • Trial status • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

Regorafenib and XmAb20717 in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy (RX-CROME) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=16 ➔ 0 | Trial completion date: Dec 2026 ➔ Feb 2024 | Initiation date: Nov 2024 ➔ May 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2024 ➔ Feb 2024

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Phase II Clinical Trial to Evaluate Safety and Efficacy of XmAb20717 in Advanced Rare Cancers (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Endocrine Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • MSI

XmAb20717 in Advanced Biliary Tract Cancers (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NTRK

Study of Vudalimab or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced NSCLC (clinicaltrials.gov) - P1/2 | N=168 | Recruiting | Sponsor: Xencor, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Regorafenib and XmAb20717 in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy (RX-CROME) (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Initiation date: Nov 2023 ➔ Nov 2024

Trial initiation date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of Vudalimab or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced NSCLC (clinicaltrials.gov) - P1/2 | N=168 | Not yet recruiting | Sponsor: Xencor, Inc.

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Xencor Reports Third Quarter 2023 Financial Results (Businesswire) - "Pipeline Updates: Vudalimab (PD-1 x CTLA-4):...Xencor anticipates initiating a Phase 1b/2 study to evaluate vudalimab...in combination with chemotherapy, as a first-line treatment in patients with advanced non-small cell lung cancer, by the end of 2023.....Xencor has been evaluating vudalimab in ongoing studies, as a monotherapy in patients with high-risk metastatic castration-resistant prostate cancer (mCRPC) and in gynecologic tumors, and in combination with chemotherapy or a PARP inhibitor in patients with mCRPC. Due to the rapidly changing competitive environment in these indications, the Company has closed the gynecologic tumor cohorts in the monotherapy study. Prostate cancer clinical data are anticipated to be presented at a medical conference in early 2024."

New P1/2 trial • P2 data • Trial status • Cervical Cancer • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Prostate Cancer