MEDI4276 / AstraZeneca - LARVOL DELTA

Emerging new treatments in HER2 positive breast cancer (SG-BCC 2023) - P1 | "Trastuzumab deruxtecan (T-DXd) was approved in December 2022 by the FDA for patients with pretreated HER2- positive breast cancer based on the results of the phase III trial Destiny-Breast03 [3], showing an impressive improvement in progression-free survival with an hazard ratio of 0.33 (95% CI 0.26– 0.43, p-value<0.0001) compared to T-DM1, according to the last update presented at SABCS 2022 [4]...Besides T-DXd and SYD985, other ADCs have been or are under investigation, including, but not limited to, patritumab deruxtecan, disitamab vedotin, XMT-1522, MM-302, MEDI-4276, A166, ARX788, BAT8001 and PF-06804103...Several TKIs have been successfully developed, with tucatinib being the latest to enter clinical practice based on the results of the HER2CLIMB trial [7], with particular importance for patients with brain metastases. Other promising emerging treatments targeting HER2/3 receptors are the HER2- targeted bispecific antibodies (including, among others, KN026..."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • CDK4 • ER • HER-2 • KLRC1 • PD-L1 • PIK3CA

Messersmith Makes Sense of the Novel Approaches on the Rise in GI Malignancies (OncLive) - "The heterogeneity of tumors in GI cancers continues to pose a challenge, according to Messersmith. As such, understanding how circulating tumor DNA will play into the management of patients as RAS inhibitors emerge in the clinic will be an area of interest going forward, Messersmith added."

Media quote

First-in-Human, Phase 1 Dose-Escalation Study of Biparatopic Anti-HER2 Antibody-Drug Conjugate MEDI4276 in Patients with HER2+ Advanced Breast or Gastric Cancer. (PubMed, Mol Cancer Ther) - "In the as-treated population, there was 1 complete response (0.5 mg/kg; BC), and 2 partial responses (0.6 and 0.75 mg/kg; BC)-all had prior trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). MEDI4276 has demonstrable clinical activity but displays intolerable toxicity at doses >0.3 mg/kg."

Clinical • Journal • P1 data • Breast Cancer • Fatigue • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors. (clinicaltrials.gov) - P1/2; N=47; Active, not recruiting; Sponsor: MedImmune LLC; Trial completion date: Oct 2019 ➔ Jul 2018; Trial primary completion date: Oct 2019 ➔ Jul 2018

Trial completion date • Trial primary completion date • Biosimilar • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2. (PubMed, Antibodies (Basel)) - P1/2; "Additional stability experiments confirmed that quantification of the released warhead in the presence of high concentrations of MEDI4276 was acceptable. Subsequently, the assays were employed in support of a first-in-human clinical trial (NCT02576548)."

Clinical • Journal

HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. (PubMed, Int J Mol Sci) - "Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522."

Journal • Review