tavolixizumab (MEDI0562) / AstraZeneca - LARVOL DELTA

Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Providence Health & Services | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Providence Health & Services | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jul 2023 ➔ Jun 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MEDI0562, a humanized OX40 agonist monoclonal antibody (mAb), increases T cell effector function and depletes regulatory T cells in blood and tumor (SITC 2018) - P1; "Conclusions MEDI0562-treated patients exhibited increased Ki67+CD4+ and CD8+ memory T cells in the periphery and decreased intratumoral OX40+FOXP3+ cells, consistent with the hypothesized dual MOA of this agonist mAb. The enhancement of these pharmacodynamic effects in patients with high OX40 levels at baseline may help identify patients or indications where MEDI0562 could provide clinical benefit."

IO biomarker • PD(L)-1 Biomarker • Bladder Cancer • Cervical Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Solid Tumor • Urothelial Cancer

A phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of the OX40 agonist MEDI0562 in combination with tremelimumab or durvalumab in adult aubjects with advanced solid tumors. (ASCO 2017) - P1; "Antitumor efficacy will be assessed as OR, disease control, duration of response, PFS, and OS using RECIST Version 1.1. Subjects will remain on treatment until unacceptable toxicity, progressive disease or other reasons for discontinuation."

Combination therapy • P1 data • Biosimilar • Immune Modulation • Inflammation • Leukemia

[VIRTUAL] Safety and tolerability of MEDI0562 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. (ASCO 2020) - P1 | "Background: We report safety and tolerability of MEDI0562, a humanized IgG1κ OX40 monoclonal antibody (mAb), in combination with durvalumab (durva; anti-PD-L1 mAb) or tremelimumab (treme; anti-CTLA-4 mAb) in patients (pts) with previously treated advanced solid tumors. The safety profile of MEDI0562 in combination with durva or treme was similar between groups. Clinical activity was observed with MEDI0562 + durva in pts with advanced solid tumors. Research Funding: AstraZeneca"

Clinical • Combination therapy • Dermatology • Fatigue • Oncology • Pruritus • Renal Disease • Solid Tumor • TNFRSF4

Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Providence Health & Services | Trial primary completion date: Jul 2022 ➔ Jul 2023

Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Safety and tolerability of MEDI0562, an OX40 agonist monoclonal antibody, in combination with durvalumab or tremelimumab in adult patients with advanced solid tumors. (PubMed, Clin Cancer Res) - "Following dose escalation, moderate toxicity was observed in both treatment arms, with no clear efficacy signals demonstrated."

Combination therapy • Journal • Immunology • Oncology • Solid Tumor • CD4 • CD8 • FOXP3

NSGO: Trial in Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P2; N=25; Completed; Sponsor: Nordic Society of Gynaecological Oncology - Clinical Trials Unit; Recruiting ➔ Completed; N=75 ➔ 25; Trial completion date: Sep 2023 ➔ Sep 2021; Trial primary completion date: Mar 2023 ➔ Jun 2021

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Safety and clinical activity of MEDI0562, a humanized OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors (ESMO 2018) - P1; "MEDI0562 was generally well tolerated in adult pts with advanced solid tumors and exhibited clinical and pharmacological activity. Based on the ADA data, a suggested MEDI0562 Phase 2 dose of ≥ 3 mg/kg Q2W was selected. 1."

Clinical • Bladder Cancer

Study of MEDI0562 Prior to Surgical Resection in Head and Neck Squamous Cell Carcinoma (HNSCC) or Melanoma (clinicaltrials.gov) - P1; N=35; Active, not recruiting; Sponsor: Providence Health & Services; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NSGO: Trial in Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P2; N=75; Recruiting; Sponsor: Nordic Society of Gynaecological Oncology - Clinical Trials Unit; Trial primary completion date: Mar 2020 ➔ Mar 2023

Clinical • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • CD73

NSGO: Trial in Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P2; N=75; Recruiting; Sponsor: Nordic Society for Gynaecologic Oncology; Trial completion date: Sep 2022 ➔ Sep 2023; Initiation date: Mar 2018 ➔ Jun 2018; Trial primary completion date: Mar 2019 ➔ Mar 2020

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD73

NSGO: Trial in Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P2; N=75; Recruiting; Sponsor: Nordic Society for Gynaecologic Oncology; Not yet recruiting ➔ Recruiting; Initiation date: Nov 2017 ➔ Mar 2018

Clinical • Enrollment open • Trial initiation date • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD73

OX40 agonists for cancer treatment: a patent review. (PubMed, Expert Opin Ther Pat) - "United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists."

Journal • Immune Modulation • Inflammation • Oncology

Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients With Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pre-treated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing."

Clinical • Journal • Fatigue • Head and Neck Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

AstraZeneca: Q3 FY 2016 Results (AstraZeneca) - Anticipated completion of enrollment in P1 trial (NCT02318394) for advanced malignancies in 2017; Anticipated completion of enrollment in P1 trial (NCT02705482) of durvalumab/tremelimumab + MEDI0562 in advanced malignancies in 2018

Anticipated enrollment status • Oncology

MEDI0562 + Imfinzi/tremelimumab: Data from P1 trial (NCT02318394) in advanced malignancies in 2020 (AstraZeneca) - Q3 FY2017 Results: Data from P1 trial (NCT02705482) in advanced malignancies in 2021

P1 data • Oncology

A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=58; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2020 ➔ Oct 2019; Trial primary completion date: Apr 2020 ➔ Oct 2019

Enrollment closed • Trial completion date • Trial primary completion date • Biosimilar • Leukemia • Oncology • Solid Tumor

AstraZeneca: H1 FY 2016 Results (AstraZeneca) - Anticipated top-line data from P1 trial (NCT02318394) of durvalumab/tremelimumab + MEDI0562 for advanced malignancies in 2017; Anticipated completion of enrollment of P1 trial (NCT02221960) of durvalumab + MEDI6383 for advanced malignancies in H2 2016; Anticipated completion of enrollment of P1 trial (NCT02503774) of durvalumab + MEDI9447 for advanced malignancies in 2018; Anticipated top-line data from P1 trial (NCT02503774) of durvalumab + MEDI9447 for advanced malignancies in 2019

Anticipated enrollment status • Anticipated P1 data • Oncology

MEDI0562 + Imfinzi/tremelimumab: Data from P1 trial (NCT02705482) in advanced malignancies in 2020 (AstraZeneca) - Q3 2018 Results

P1 data • Oncology

A Phase 1 Study of MEDI0562 in Adult Subjects With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1; N=50; Not yet recruiting; Sponsor: MedImmune LLC

Clinical • IO Biomarker • New P1 trial • P1 data

A Phase 1 Study of MEDI0562 in Adult Subjects With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1; N=56; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed; Trial primary completion date: Mar 2020 ➔ Jan 2018

Clinical • IO Biomarker • Trial completion • Trial primary completion date

Agonist redirected checkpoint, PD1-Fc-OX40L, for cancer immunotherapy. (PubMed, J Immunother Cancer) - "High binding affinity on both sides of the construct translated to potent stimulation of OX40 signaling and PD1:PD-L1/L2 blockade, in multiple in vitro assays, including improved potency as compared to pembrolizumab, nivolumab, tavolixizumab and combinations of those antibodies. Importantly, all agonist functions of PD1-Fc-OX40L are independent of Fc receptor cross-linking. Collectively, these data demonstrate a highly potent fusion protein that is part of a platform, capable of providing checkpoint blockade and TNFRSF costimulation in a single molecule, which uniquely localizes TNFRSF costimulation to checkpoint ligand positive tumor cells."

Journal