BMS-986288 / BMS, CytomX - LARVOL DELTA

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=219 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | N=494 ➔ 219 | Trial completion date: May 2025 ➔ Aug 2024

Combination therapy • Enrollment change • Metastases • Trial completion • Trial completion date • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=494 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Jun 2024 ➔ Oct 2024

Combination therapy • Metastases • Trial primary completion date • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=494 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Oncology • Solid Tumor

Preclinical characterization of BMS-986288, a novel non‑fucosylated (NF) anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4) Probody® therapeutic (AACR 2024) - P1/2 | "Introduction: Blockade of the CTLA-4 pathway with ipilimumab (IPI), alone and in combination with nivolumab (anti-programmed death-1 antibody), has shown clinical benefit in multiple tumor types. BMS-986288 leverages unique characteristics to differentiate it from IPI, enhancing APC-mediated T-cell priming and anti-tumor activity while also reducing peripheral activity in preclinical models. These data support an ongoing phase 1/2 clinical trial of BMS-986288 (NCT03994601) in patients with advanced solid tumors."

IO biomarker • Preclinical • Oncology • Solid Tumor

CytomX Therapeutics Reports 2023 Financial Results and Provides Business Update (GlobeNewswire) - "The anti-CTLA-4 PROBODY BMS-986288 will not be further advanced following a recent BMS internal portfolio review....Following a corporate portfolio prioritization process, Bristol Myers Squibb (BMS) notified CytomX on March 6th, 2024 that it does not intend to continue the development of BMS-986288 beyond the current Phase 2 study."

Discontinued • Solid Tumor

CytomX Therapeutics Outlines 2024 Company Priorities and Milestones (GlobeNewswire) - "Next-Generation CTLA-4 Program: Continued clinical progress for BMS-986288 including proof-of-concept studies in MSS CRC and NSCLC. Bristol Myers Squibb anticipates data from the study will be available in 2024."

P1/2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CytomX Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Preclinically, Probody^® IFN-a2b has demonstrated a widened predicted therapeutic index with an improved tolerability profile compared to unmasked interferon alpha-2b, including preferential anti-cancer activity in the tumor microenvironment and increased anti-tumor effects when combined with checkpoint inhibitors. In November 2023, at the Society for Immunotherapy for Cancer (SITC) 38th Annual Meeting, additional preclinical data were presented demonstrating enhancement of PD-1 anti-tumor efficacy and inflammation of the tumor microenvironment by Probody IFN-a2b. An IND filing for CX-801 is expected by the end of 2023 with planned clinical initiation in 2024....The Phase 2 clinical evaluation of BMS-986288 is ongoing and includes proof of concept studies for microsatellite stable (MSS) colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). BMS anticipates data from the study will be available in 2024."

IND • New trial • P2 data • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CytomX Therapeutics Reports First Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "First Quarter Business Highlights and Recent Developments: (i) BMS advancement of BMS-986288 to Phase 2 - In February 2023, BMS published pipeline updates that included moving the Anti-CTLA-4 non-fucosylated Probody®, BMS-986288, from Phase 1 to Phase 2; (ii) CD71-Targeting strategies under evaluation - In March 2023, AbbVie notified CytomX that it would not advance the CD71-targeting, conditionally activated ADC, CX-2029, into additional clinical studies and provided notice of termination of the 2016 CD71 License and Collaboration Agreement."

Licensing / partnership • Phase shift • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=494 | Recruiting | Sponsor: Bristol-Myers Squibb | N=344 ➔ 494

Combination therapy • Enrollment change • Metastases • Oncology • Solid Tumor

CytomX Therapeutics Provides Business Update and Outlines 2023 Company Priorities (GlobeNewswire) - "2023 KEY MILESTONES AND OUTLOOK...CX-2029 (CD71): Determine next steps with AbbVie; BMS CTLA-4: Continued clinical progress on BMS-986249 and BMS-986288; Collaborations: Initiation of R&D activities with our newest collaborators, Regeneron and Moderna."

Pipeline update • Oncology • Solid Tumor

[VIRTUAL] Preclinical characterization of novel anti-CTLA-4 prodrug antibodies with an enhanced therapeutic index (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...Here, we describe the preclinical characterization of 2 novel anti–CTLA-4 PB mAbs: anti–CTLA-4 PB (BMS-986249) is a peptide-masked version of IPI, and anti‒CTLA-4 nonfucosylated (NF) PB (BMS-986288) is a peptide-masked version of anti–CTLA-4 NF, which has enhanced antibody-dependent cellular cytotoxicity (ADCC) and regulatory T-cell (Treg) depletion compared with IPI. Antibody binding to CD16 was studied by surface plasmon resonance... These data demonstrate the potential of the PB-Tx technology platform to improve the therapeutic indices of anti–CTLA-4 PB and anti–CTLA-4 NF PB relative to their parental mAbs. The safety and antitumor activity of anti–CTLA-4 PB (NCT03369223) and anti–CTLA-4 NF PB (NCT03994601) are being investigated in patients with advanced solid cancers in ongoing phase..."

IO Biomarker • 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

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

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=344 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Apr 2024 ➔ May 2025 | Trial primary completion date: Sep 2023 ➔ Apr 2024

Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2; N=344; Recruiting; Sponsor: Bristol-Myers Squibb; N=200 ➔ 344; Trial primary completion date: Feb 2023 ➔ Sep 2023

Combination therapy • Enrollment change • Trial primary completion date • Oncology • Solid Tumor

"Next gen Fc-engineered or non-fucosylated anti-CTLA4 (zalifrelimab, BMS-986288, XTX101 etc) may actually deplete Tregs in a meanginful way and may have a differentiated mechanism. Based on early hints, there might be a monotherapy role. No role for ipilimumab mono moving forward." (@jasonlukemd)

Monotherapy

CytomX Therapeutics Announces Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - "BMS-986249: Anti-CTLA-4 Probody Immunotherapeutic. Bristol Myers Squibb continues to enroll patients as part of the Part 2a randomized cohort expansion of the ongoing Phase 1/2a trial of BMS-986249 administered in combination with nivolumab (Opdivo®) in patients with metastatic melanoma....BMS-986288: Anti-CTLA-4 Non-Fucosylated Probody Immunotherapeutic. Bristol Myers Squibb continues to enroll patients as part of the Part 1 dose escalation study of the ongoing Phase 1/2a trial of BMS-986288 administered as monotherapy and in combination with nivolumab in patients with selected advanced solid tumors."

Enrollment status • Hematological Malignancies • Melanoma • Oncology • Solid Tumor

CytomX Therapeutics Announces Preclinical Data from Anti-CTLA-4 Probody Therapeutic Programs Presented by Partner Bristol Myers Squibb at AACR Annual Meeting (GlobeNewswire) - "CytomX Therapeutics, Inc...announced that its partner Bristol Myers Squibb presented preclinical data from BMS-986249 and BMS-986288, anti-CTLA-4 Probody therapeutics generated with CytomX’s novel Probody® technology platform. The electronic poster #4551 titled 'Preclinical characterization of novel anti-CTLA-4 prodrug antibodies with an enhanced therapeutic index' was presented as part of the Therapeutic Antibodies 3 Session at the American Association of Cancer Research’s (AACR) 2020 Virtual Annual Meeting II."

Preclinical • Oncology • Solid Tumor

An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Solid Cancers (clinicaltrials.gov) - P1/2; N=200; Recruiting; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open