BMS-986218 / BMS - LARVOL DELTA

Neo-Red-P: Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Columbia University | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Study of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Bristol-Myers Squibb | Completed ➔ Terminated; Business objectives have changed

Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies (clinicaltrials.gov) - P1/2 | N=13 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2025 ➔ May 2027 | Trial primary completion date: May 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Endocrine Cancer • Liver Cancer • Lung Cancer • Oncology • Solid Tumor

Neoadjuvant androgen deprivation therapy with or without Fc-enhanced non-fucosylated anti-CTLA-4 (BMS-986218) in high risk localized prostate cancer: a randomized phase 1 trial. (PubMed, medRxiv) - "Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming. In total, this study provides the first-in-human evidence of Treg depletion by glycoengineered antibodies targeting CTLA-4 in humans and their potential in combination with ADT in prostate cancer patients with high-risk of recurrence."

Journal • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FCGR3A

Efficacy and immunological correlates of response to neoadjuvant afucosylated anti-CTLA-4 (BMS-986218) in combination with androgen deprivation therapy in high-risk localized prostate cancer (CRI-ENCI-AACR ICIC 2024) - P1 | " NeoRED-P is a single-center, two-arm, open-label pilot study assessing degarelix (ADT) versus ADT + anti-CTLA4-NF (BMS-986218) in patients with high-risk localized prostate cancer. The neoadjuvant combination of ADT + anti-CTLA4-NF (BMS-986218) is feasible, well tolerated, and induces significant remodeling of the prostate immune microenvironment through both canonical and novel mechanisms. Rates of disease recurrence following surgery were low in this high-risk population, and correlative studies identified immune signatures associated with response. These findings identify mechanisms by which anti-CTLA4-NF augments antitumor immunity in the prostate and support further investigation of combination immuno-hormonal therapy in the neoadjuvant setting for high-risk prostate cancer."

Clinical • Combination therapy • IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • ENTPD1 • FCGR3A

[PREPRINT] Neoadjuvant androgen deprivation therapy with or without Fc-enhanced non-fucosylated anti-CTLA-4 (BMS-986218) in high risk localized prostate cancer: a randomized phase 1 trial (medRxiv) - P0 | N=26 | NCT04301414 | "Treatment was well tolerated and feasible in the neoadjuvant setting. A secondary clinical outcome was the rate of disease recurrence, which was lower than predicted in both arms. Mechanistically, anti-CTLA4-NF reduced ADT-induced Treg accumulation through engagement of CD16a/FCGR3A on tumor macrophages, and depth of Treg depletion was quantitatively associated with clinical outcome. Increased intratumoral dendritic cell (DC) frequencies also associated with lack of recurrence, and pre-clinical data suggest ADCC/P-competent anti-CTLA-4 antibodies elicit activation and expansion of tumor DCs. Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming."

Clinical data • Preprint • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Neo-Red-P: Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Columbia University | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies (clinicaltrials.gov) - P1/2 | N=13 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2024 ➔ May 2025 | Trial primary completion date: May 2024 ➔ May 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Endocrine Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=512 | Terminated | Sponsor: Bristol-Myers Squibb | N=390 ➔ 512 | Active, not recruiting ➔ Terminated; Business Objectives have changed.

Combination therapy • Enrollment change • Metastases • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Efficacy and immunological outcomes of non-fucosylated anti-CTLA-4 (BMS-986218) + degarelix acetate vs. degarelix acetate alone in men with high-risk localized prostate cancer (Neo-Red-P) (AACR 2024) - P1 | "The neoadjuvant combination of ADT + aCTLA-4-NF (BMS-986218) is feasible, well tolerated, and induces significant remodeling of the immune TME through enhanced Fc receptor and CTL activity. Rates of disease recurrence following surgery were low in this high-risk population, warranting further investigation of combination immuno-hormonal therapy in the neoadjuvant setting for high-risk prostate cancer.Clinical Trial Information: NCT04301414"

Clinical • IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8

First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=390 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Dec 2023 ➔ Apr 2024

Combination therapy • Metastases • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed | N=204 ➔ 10

Combination therapy • Enrollment change • Metastases • Trial completion • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Feb 2026 ➔ Dec 2023 | Trial primary completion date: Feb 2026 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Neo-Red-P: Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Columbia University | Recruiting ➔ Active, not recruiting | Trial completion date: May 2024 ➔ Jun 2025 | Trial primary completion date: May 2023 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=390 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TSLP

[VIRTUAL] First-in-human phase 1/2a study of the novel nonfucosylated anti–CTLA-4 monoclonal antibody BMS-986218 ± nivolumab in advanced solid tumors: initial phase 1 results (SITC 2020) - P1/2 | "Background CTLA-4 pathway blockade with ipilimumab (IPI) ± nivolumab (NIVO; anti–PD-1) is an effective treatment for several cancers. Preliminary pharmacodynamic activity was consistent with enhanced effects of CTLA-4 blockade. Data from continuing dose escalation of BMS-986218 ± NIVO along with preclinical results provide support for ongoing monotherapy expansions and for BMS-986218 + NIVO expansions in patients with advanced cancer."

IO biomarker • P1/2 data • Oncology • Solid Tumor • CD8

[VIRTUAL] Preclinical characterization of BMS-986218, a novel nonfucosylated anti‒CTLA-4 antibody designed to enhance antitumor activity (AACR-II 2020) - P1/2 | "Background: Blockade of the CTLA-4 pathway with ipilimumab (IPI) as monotherapy or in combination with nivolumab (anti–PD-1) is an effective treatment for a variety of cancers. Nonfucosylation of an anti–CTLA-4 antibody increased binding affinity to CD16, induced depletion of Tregs while increasing T-effector cells in mouse tumors, and enhanced tumor growth inhibition in a dose-dependent manner, thus demonstrating improved ADCC compared with IPI. An ongoing phase 1/2 study is evaluating the safety and antitumor activity of anti–CTLA-4 NF alone and in combination with nivolumab (NCT03110107) in patients with advanced solid cancers."

Preclinical • Oncology • Solid Tumor • FOXP3 • IL2

Phase 1/2a study of the novel nonfucosylated anti-CTLA-4 monoclonal antibody BMS-986218 +- nivolumab in advanced solid tumors: part 1 results (SITC 2022) - P1/2 | "In preclinical models, BMS-986218 increased the proportion of antigen-specific CD8+ effector T cells vs ipilimumab in peripheral blood. These results support further investigation of nonfucosylated anti-CTLA-4 therapies. The dose expansion part of the BMS-986218 ± nivolumab study and a phase 1/2 study evaluating anti–CTLA-4 nonfucosylated probody (BMS-986288; NCT03994601 ) ± nivolumab are ongoing."

P1/2 data • Breast Cancer • Gastric Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CXCL10 • CXCL9 • IFNG

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies (clinicaltrials.gov) - P1/2 | N=13 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=80 ➔ 13

Combination therapy • Enrollment change • Enrollment closed • IO biomarker • Endocrine Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

CytomX Therapeutics Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Third Quarter Business Highlights and Recent Developments:...Additionally, at the SITC annual meeting, a poster presentation will be presented by Bristol Myers Squibb titled 'Phase 1/2a study of the novel nonfucosylated anti-CTLA monoclonal antibody BMS-986218 ± nivolumab in advanced solid tumors: Part 1 results,' focused on BMS-986218, the non-masked version of BMS-986288. This presentation includes preclinical data on BMS-986288."

P1/2 data • Preclinical • Oncology • Solid Tumor

First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=390; Recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: Nov 2023 ➔ Jun 2024; Trial primary completion date: Mar 2023 ➔ Dec 2023

Combination therapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P2; N=204; Not yet recruiting; Sponsor: Bristol-Myers Squibb

Clinical • Combination therapy • New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MRI

[VIRTUAL] First-in-human phase 1/2a study of the novel nonfucosylated anti–CTLA-4 monoclonal antibody BMS-986218 ± nivolumab in advanced solid tumors: initial phase 1 results (SITC 2020) - P1/2 | "Background CTLA-4 pathway blockade with ipilimumab (IPI) ± nivolumab (NIVO; anti–PD-1) is an effective treatment for several cancers. Preliminary pharmacodynamic activity was consistent with enhanced effects of CTLA-4 blockade. Data from continuing dose escalation of BMS-986218 ± NIVO along with preclinical results provide support for ongoing monotherapy expansions and for BMS-986218 + NIVO expansions in patients with advanced cancer."

IO biomarker • P1/2 data • Oncology • Solid Tumor • CD8

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies (clinicaltrials.gov) - P1/2; N=80; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • IO biomarker • Endocrine Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor