MEDI5083 / AstraZeneca - LARVOL DELTA

A phase 1 study of the CD40 agonist MEDI5083 in combination with durvalumab in patients with advanced solid tumors. (PubMed, Immunotherapy) - "MEDI5083 maximum tolerated dose was 5 mg. Objective response rate was 2.8% (1 partial response and 11 stable disease). MEDI5083 toxicity profile limits its further development."

Combination therapy • Journal • Metastases • P1 data • Fatigue • Oncology • Solid Tumor • CD40

First-in-human study of CD40 agonist MEDI5083 in advanced solid tumors with durvalumab administered sequentially or concurrently (SITC 2019) - "Subcutaneous administration of MEDI5083 caused high rates of injection site reactions. The toxicity profile does not support further development of the subcutaneous formulation of this drug."

P1 data

MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel. (clinicaltrials.gov) - P1; N=39; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen-presenting cells and promotes robust anti-tumor immune responses in both hot and cold murine tumor models (AACR-II 2020) - "We have demonstrated that stimulation of CD40 signaling with MEDI5083 or mCD40L-Fc leads to robust activation of immune cells and enhanced adaptive immune responses. In vivo, this translates to enhanced control of both poorly- and well-infiltrated syngeneic tumors and generation of durable memory in mice with complete tumor regression."

IO Biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD40LG • IFNG • IL12A

MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel. (clinicaltrials.gov) - P1; N=38; Active, not recruiting; Sponsor: MedImmune LLC; Trial completion date: Jan 2020 ➔ May 2020; Trial primary completion date: Jan 2020 ➔ May 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date

MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel. (clinicaltrials.gov) - P1; N=38; Active, not recruiting; Sponsor: MedImmune LLC; N=495 ➔ 38; Trial completion date: Aug 2022 ➔ Dec 2019; Trial primary completion date: Aug 2022 ➔ Dec 2019

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date

HERA-CD40L, a hexavalent CD40 agonist, induces a significant T cell mediated anti-tumor immune response and shows superior activity in direct comparison to benchmark agonistic antibodies (CIMT 2019) - "...Currently, seven different antibodies and only one CD40L-based hexavalent fusion protein (MEDI5083) are in active clinical trials...We performed extensive comparisons to multiple benchmark antibodies in development (including CP-870,893/Selicrelumab)...In summary, HERA-CD40L is a potent agonist able to shows single agent anti-tumor activity both in vitro and in vivo. The MoA is well defined and the biological activity is distinct from and superior to clinical benchmark “agonistic” antibodies."

IO Biomarker

HERA-CD40L, a hexavalent CD40 agonist, induces a significant T cell mediated anti-tumor immune response and shows superior activity in direct comparison to benchmark agonistic antibodies (CIMT 2019) - "...Currently, seven different antibodies and only one CD40L-based hexavalent fusion protein (MEDI5083) are in active clinical trials...We performed extensive comparisons to multiple benchmark antibodies in development (including CP-870,893/Selicrelumab)...In summary, HERA-CD40L is a potent agonist able to shows single agent anti-tumor activity both in vitro and in vivo. The MoA is well defined and the biological activity is distinct from and superior to clinical benchmark “agonistic” antibodies."

IO Biomarker

MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel. (clinicaltrials.gov) - P1; N=495; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting; N=204 ➔ 495

Clinical • Combination therapy • Enrollment change • Enrollment closed

MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen presenting cells and promotes a robust anti-tumor immune response in a B16F10 murine tumor model (AACR 2019) - "Thus, mCD40L-Fc elicits robust immune activation and significant anti-tumor activity against B16F10 tumors, which have low responsiveness to checkpoint inhibitors. The insights obtained from the preclinical studies support the development of MEDI5083, which is currently in clinical development for a broad spectrum of malignancies."

Preclinical