2141-V11 / Memorial Sloan-Kettering Cancer Center, Rockefeller University - LARVOL DELTA

MGMT unmethylated, newly diagnosed glioblastoma (ndGBM) patients treated with D2C7-IT and a CD40 agonist (2141-V11) via convection-enhanced delivery (CED) followed by cervical perilymphatic injections (CPLI) of 2141-V11 (SNO 2026) - No abstract available

Clinical • Brain Cancer • Glioblastoma • Solid Tumor • CD40 • MGMT

Safety and feasibility of the Tumor Monorail Device (TMD) for serial tumor sampling at bedside in a trial of intratumoral D2C7-IT and an Fc-engineered anti-humanCD40 monoclonal antibody (2141-V11) administered via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients (SNO 2026) - No abstract available

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

A Study of 2141-V11 in People With Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1/2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Phase I study of intravesical Fc-optimized anti-CD40 agonist antibody 2141-V11 for non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) therapy (AACR 2024) - P1 | "As of the data cutoff on 12/20/23, 80% of the planned patients (n=20) have been enrolled, with no dose-limiting toxicities observed. Accrual completion is expected by the first quarter of 2024, with ongoing analysis of urine immune profiling, cytokine analysis, as well as single-cell spatial phenotyping in pre- and post-treatment samples."

First-in-human • IO biomarker • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD40LG

Fc-optimized anti-CD40 agonist antibody 2141-V11 for BCG-unresponsive non-muscle invasive bladder cancer: Updates on phase 1 study clinical outcomes and biological correlatives (AACR 2025) - P1 | "In patients with BCG-unresponsive NMIBC, intravesical administration of 2141-V11 is safe and leads to CR in a subset of patients. 2141-V11 promotes immune interactions among dendritic cells and distinct subsets of CD8+ T cells and is associated with increased presence of TLS in clinical responders. These findings provide biological rationale for further evaluation of this agent in the treatment of NMIBC."

Clinical • Clinical data • First-in-human • IO biomarker • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD8 • CXCL13

Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment (clinicaltrials.gov) - P1/2 | N=115 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Phase classification: P1 ➔ P1/2 | N=55 ➔ 115

Enrollment change • Phase classification • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Darell Bigner | Trial completion date: Jun 2027 ➔ Jun 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor

Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment (clinicaltrials.gov) - P1 | N=55 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2026 ➔ Nov 2027 | Trial primary completion date: Nov 2026 ➔ Nov 2027

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

A Study of 2141-V11 in Combination With Standard Treatments in People With Prostate Cancer (clinicaltrials.gov) - P2 | N=57 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | N=99 ➔ 57

Enrollment change • Monotherapy • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • CD4

An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients (SNO 2025) - P1 | " Eligibility include adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; KPS ≥70%, and an area of non-enhancing disease amenable for TMD implantation. Enrollment, safety and results from the repeated TMD collection will be updated."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Investigation of the combination of D2C7-IT with an Fc-engineered anti-humanCD40 monoclonal antibody (2141-V11) when administered intratumorally via convection-enhanced delivery (CED) followed by cervical perilymphatic injections (CPLIs) of 2141-V11 compared to D2C7-IT CED monotherapy in patients with recurrent glioblastoma (rGBM) (SNO 2025) - P1 | " Eligibility included adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. The addition of CPLIs of 2141-V11 post CED of D2C7-IT+2141-V11 is feasible, shows an acceptable toxicity profile, and has a survival advantage compared to D2C7-IT monotherapy."

Clinical • Monotherapy • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8

An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients (SNO 2025) - P1 | " Eligibility include adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; KPS ≥70%, and an area of non-enhancing disease amenable for TMD implantation. Enrollment, safety and results from the repeated TMD collection will be updated."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients (WFNOS 2025) - P1 | " Eligibility include adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; KPS ≥70%, and an area of non-enhancing disease amenable for TMD implantation. Enrollment, safety and results from the repeated TMD collection will be updated."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Investigation of the combination of D2C7-IT with an Fc-engineered anti-humanCD40 monoclonal antibody (2141-V11) when administered intratumorally via convection-enhanced delivery (CED) followed by cervical perilymphatic injections (CPLIs) of 2141-V11 compared to D2C7-IT CED monotherapy in patients with recurrent glioblastoma (rGBM) (WFNOS 2025) - P1 | " Eligibility included adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. The addition of CPLIs of 2141-V11 post CED of D2C7-IT+2141-V11 is feasible, shows an acceptable toxicity profile, and has a survival advantage compared to D2C7-IT monotherapy."

Clinical • Monotherapy • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Glioma • Solid Tumor • CD8

An assessment of the Tumor Monorail Device (TMD) for repeated sampling as part of a trial evaluating the combination of D2C7-IT and an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) and cervical perilymphatic injections (CPLIs) of 2141-V11 in recurrent glioblastoma (rGBM) patients (WFNOS 2025) - P1 | " Eligibility include adult patients with solitary supratentorial rGBM, IDH wild-type; ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; KPS ≥70%, and an area of non-enhancing disease amenable for TMD implantation. Enrollment, safety and results from the repeated TMD collection will be updated."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma

Dissecting the spatial immune structures underlying response to anti-CD40 agonist antibody 2141-V11 for BCG-unresponsive non-muscle invasive bladder cancer (CICON 2025) - P1 | "We further identified that responders had treatment-associated increase in the proportion of GZMB+ CD8+ T cells in tetrads with CD4+ T cells, B cells, and DCs, contributing to both TLS-like and non-TLS-like immune aggregates. In sum, we present a comprehensive spatial analysis framework applied to clinical samples that reveal key immune populations and interaction units driving response to the anti-CD40 agonist 2141-V11 for BCG-unresponsive NMIBC."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD21 • CD8 • CXCL13 • GZMB

Short talk | Dissecting the spatial immune structures underlying response to anti-CD40 agonist antibody 2141-V11 for BCG-unresponsive non-muscle invasive bladder cancer (CICON 2025) - No abstract available

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer. (PubMed, Res Sq) - P1 | "In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588)."

Journal • Metastases • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD40

D2C7-IT + 2141-V11 Combination Post-rection in rGBM - Phase 1b (clinicaltrials.gov) - P1/2 | N=46 | Not yet recruiting | Sponsor: Darell Bigner

New P1/2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment (clinicaltrials.gov) - P1 | N=55 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | N=25 ➔ 55 | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Enrollment change • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Phase I study of intravesical Fc-optimized anti-CD40 agonist antibody 2141-V11 for non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) (AUA 2024) - P1 | "Intravesical 2141-V11 is well tolerated up to 70 mg with minimal local side effects and no evidence of systemic toxicity. Completion of accrual and biological correlatives will reveal on-target activity and early efficacy data."

IO biomarker • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

AUA 2024: Phase I Study of Intravesical Fc-Optimized Anti-CD40 Agonist Antibody 2141-V11 for Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) (Urotoday) - P1 | N=25 | NCT05126472 | "Dr. Bernard Bochner presented the results of a phase 1 study of intravesical Fc-optimized anti-CD40 agonist antibody 2141-V11 for non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG)....Dr. Bochner concluded that intravesical 2141-V11 is well-tolerated with no dose-limiting toxicities observed up to 70 mg. MTD was not reached. Despite nearly half the population having a history of T1 disease prior to enrollment, 44% demonstrated a complete response at 6 months with a complete response rate of 45% at any time point. Correlative studies are ongoing to further investigate on-target activity in post-treatment specimens."

P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A Study of 2141-V11 in Combination With Standard Treatments in People With Prostate Cancer (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Combination therapy • Metastases • Monotherapy • New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1 Trial of D2C7-IT in Combination With 2141-V11 for Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Annick Desjardins, MD | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Harnessing the potential of CD40 agonism in cancer therapy. (PubMed, Cytokine Growth Factor Rev) - "In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them."

IO biomarker • Journal • Review • Oncology • CD40 • CD40LG • CD8 • TNFA