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

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

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."

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

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

Phase 1/1b trial of Fc-engineered Anti-CD40 Agonist Monoclonal Antibody (2141-V11) infused with D2C7-IT in enhancing disease by Convection-Enhanced Delivery (CED) for Recurrent Malignant Glioma (rMG) (SNO 2023) - " Eligibility includes adult patients with solitary supratentorial rMG (WHO grade 3/4); ≥ 4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. The RP2D for intratumoral infusion of D2C7-IT+2141-V11 via CED is identified. The protocol was amended to evaluate the addition of cervical perilymphatic injections of 2141-V11 post CED of D2C7-IT+2141-V11."

IO biomarker • P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Glioma • Oncology • Pain • Solid Tumor • Ventriculomegaly • CD8 • EGFR

D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Darell Bigner | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer. (PubMed, Proc Natl Acad Sci U S A) - "Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Collectively, these data reveal an important role for IL-15 in mediating antitumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to develop combinations of these promising therapeutics for the treatment of patients with bladder cancer."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD40 • CD8 • IL15

D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov) - P1/2 | N=50 | Not yet recruiting | Sponsor: Darell Bigner | Initiation date: May 2023 ➔ Aug 2023

Trial initiation date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Rockefeller University | Recruiting ➔ Completed | N=28 ➔ 16 | Trial completion date: Jul 2025 ➔ Mar 2023 | Trial primary completion date: Jul 2025 ➔ Mar 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immune Modulation • Melanoma • Oncology • Skin Cancer • Solid Tumor

Dose escalation trial of Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) administered intratumorally with D2C7-IT via Convection-Enhanced Delivery (CED) for Recurrent Malignant Gliomas (rMGs) (SNO 2022) - " Eligibility includes adult patients with solitary supratentorial rMG (WHO grade 3/4); ≥ 4 weeks after chemotherapy, bevacizumab, or study drug; adequate organ function; and KPS ≥ 70%. Intratumoral administration of D2C7-IT+2141-V11 via CED is safe, encouraging efficacy results are observed."

IO biomarker • Brain Cancer • CNS Disorders • Epilepsy • Fatigue • Glioblastoma • Glioma • Immune Modulation • Inflammation • Oncology • Pain • Solid Tumor • CD40 • EGFR

D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients (clinicaltrials.gov) - P1/2 | N=50 | Not yet recruiting | Sponsor: Darell Bigner

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

Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2023 ➔ Nov 2024 | Trial primary completion date: Nov 2023 ➔ Nov 2024

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