D2C7 / Istari Oncology, Duke University - LARVOL DELTA

D2C7-IT With Atezolizumab for Recurrent Gliomas (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Darell Bigner | Trial primary completion date: Dec 2025 ➔ Jun 2024

Trial primary completion date • Brain Cancer • Glioma • Malignant Glioma • Oncology • Solid Tumor

D2C7-IT With Atezolizumab for Recurrent Gliomas (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Darell Bigner | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Solid Tumor

D2C7-IT + 2141-V11 Combination Post-resection in RGBM (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: Darell Bigner | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Glioblastoma • 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 | N=30 ➔ 90 | Trial completion date: Dec 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Hematological Disorders • Malignant Glioma • Oncology • Solid Tumor

D2C7-IT + 2141-V11 Combination Post-resection in RGBM (clinicaltrials.gov) - P1 | N=46 | Not yet recruiting | Sponsor: Darell Bigner | Initiation date: Nov 2024 ➔ Mar 2025

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

D2C7-IT in combination with an Fc-engineered anti-humanCD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery (CED) followed by cervical perilymphatic injections (CPLIs) of 2141-V11 in patients with recurrent glioblastoma (rGBM) (SNO 2024) - P1 | " Eligible are adult patients with solitary supratentorial rGBM; ≥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 and has shown an acceptable toxicity profile. The safety and efficacy results will be updated."

Clinical • Combination therapy • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Glioblastoma • Oncology • Pain • Solid Tumor • Ventriculomegaly • CD8

VEGF inhibition improves immunotoxin and αCD40 antitumor response in glioblastoma models (SITC 2024) - "Background D2C7-immunotoxin (D2C7-IT) is a cytotoxic therapy against glioblastoma (GBM) that effectively induces tumor cell-killing by targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, two major oncogenes in GBM...Conclusions Inhibition of VEGF improved D+C-induced antitumor responses in advanced murine gliomas by increasing CD4+ T cell and B cell recruitment. Future CD4+ T cell and B cell in vivo depletion and in vitro functional studies will confirm the mechanism behind D+C+V-mediated antitumor response."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD40 • CD8 • EGFR

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

Phase classification • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

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

D2C7 for Adult Patients With Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: Darell Bigner | Trial completion date: Oct 2022 ➔ Mar 2024

Trial completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

D2C7 for Adult Patients With Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: Darell Bigner | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

D2C7 for Adult Patients With Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=81 | Active, not recruiting | Sponsor: Darell Bigner | Trial completion date: Jan 2024 ➔ Jul 2024

Trial completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

D2C7-IT With Atezolizumab for Recurrent Gliomas (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Annick Desjardins, MD | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

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

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

".@ADesjardinsMD reporting on a trial intratumoral administration of D2C7-IT, an immunotoxin-based cytotoxic therapy, targeting EGFR vIII combined with a CD40 antibody with plans to include repeated cervical perilymphatic injections of the CD40Ab #ICBTRT #AsilomarToKiawah" (@Dukeneurosurg)

Immune Modulation • Oncology • CD40

A phase 1 trial of D2C7-it in combination with an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma (MG). (ASCO 2022) - P1 | " Eligibility includes adult patients with recurrence of a solitary supratentorial WHO grade 3 or 4 MG; ≥ 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, and encouraging efficacy results have been observed."

Clinical • Combination therapy • IO biomarker • P1 data • Brain Cancer • Glioma • Immune Modulation • Inflammation • Oncology • Pain • Solid Tumor • CD40 • CD8

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 With Atezolizumab for Recurrent Gliomas (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Darell Bigner | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Dec 2027 | Trial primary completion date: Jan 2023 ➔ Dec 2023

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

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

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models. (PubMed, Sci Transl Med) - P1 | "D2C7-IT+αCD40 treatment stimulated intratumoral CD8 T cell proliferation and generated cures in glioma-bearing mice despite FTY720-induced peripheral T cell sequestration. To determine potential translation, immunohistochemistry staining confirmed CD40 expression in human GBM tissue sections. These promising preclinical data allowed us to initiate a phase 1 study with D2C7-IT+αhCD40 in patients with malignant glioma (NCT04547777) to further evaluate this treatment in humans."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD40 • CD8 • EGFR

[VIRTUAL] A Phase 1 Trial of D2C7-IT in Combination with Atezolizumab in Recurrent WHO Grade IV Malignant Glioma (MG) (SNO 2020) - " Eligibility includes adult patients with recurrence of a solitary supratentorial WHO grade IV MG; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS >70%. D2C7-IT monotherapy has shown prolonged survival and disease control in some patients. We are now evaluating the combination of D2C7-IT with checkpoint inhibition."

Combination therapy • IO biomarker • P1 data • Glioma • Oncology • Solid Tumor • CD8

D2C7 for Adult Patients With Recurrent Malignant Glioma (clinicaltrials.gov) - P1 | N=81 | Active, not recruiting | Sponsor: Darell Bigner | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioma • Oncology • Solid Tumor