MEDI7247 / AstraZeneca - LARVOL DELTA

ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study. (PubMed, Target Oncol) - P1 | "Thrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428)."

Journal • P1 data • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • SLC1A5

Multiplex Bioanalytical Methods for Comprehensive Characterization and Quantification of the Unique Complementarity-Determining-Region Deamidation of MEDI7247, an Anti-ASCT2 Pyrrolobenzodiazepine Antibody-Drug Conjugate. (PubMed, Antibodies (Basel)) - P1 | "The impact of deamidation on the pharmacokinetic characteristics of MEDI7247 from clinical trial NCT03106428 was analyzed, revealing a gradual reduction in the nondeamidated form of MEDI7247 in vivo. Careful quantitative biotransformation analyses of complex biotherapeutic conjugates help us understand changes in product PTMs after administration, thus providing a more complete view of in vivo pharmacology."

Journal • SLC1A5

Preclinical radiolabeling, in vivo biodistribution and positron emission tomography of a novel pyrrolobenzodiazepine (PBD)-based antibody drug conjugate targeting ASCT2. (PubMed, Nucl Med Biol) - "MEDI7247 (human anti-ASCT2 antibody conjugated with pyrrolobenzodiazepine (PBD)) and MEDI7519 (MEDI7247 without PBD drug conjugate) and an isotype control antibody drug conjugate construct were conjugated with p-isothiocyanatobenzyl-deferoxamine (Df) and radiolabeled with zirconium-89. Preclinical biodistribution analyses of [Zr]Zr-Df-MEDI7247 and [Zr]Zr-Df-MEDI7519 showed the biodistribution pattern of anti-ASCT2 ADC MEDI7247 was similar to parental MEDI7519, and both antibodies showed specific tumor uptake compared to an isotype control ADC. This study highlights an important role nuclear medicine imaging techniques can play in early preclinical assessment of drug specificity as part of the drug development pipeline."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • SLC1A5

Discovery and Development of MEDI7247, a Novel Pyrrolobenzodiazepine (PBD)-Based Antibody Drug Conjugate Targeting ASCT2, for Treating Hematological Cancers (ASH 2018) - P1; "Furthermore, MEDI7247 demonstrated acceptable safety profile in toxicity studies with non-human primates to support first in human trials. In conclusion, based on its combined efficacy and safety, MEDI7247, a first-in class ADC is currently being evaluated in clinic for the treatment of ASCT2 positive hematological malignancies (NCT03106428)."

IO biomarker • Acute Myelogenous Leukemia • Biosimilar • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A phase 1 multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of MEDI7247 in patients with select relapsed/refractory hematologic malignancies. (ASCO 2018) - P1; "The secondary objectives are to evaluate the antitumor activity (best overall response, objective response rate, time to response, duration of response, progression-free survival, and overall survival as defined in the relevant response criteria), pharmacokinetics, and immunogenicity of MEDI7247. Recruitment is ongoing for this study; as of February 6, 2018, 19 patients have been enrolled (AML, n = 11; DLBCL, n = 6; MM, n = 2) with a target enrollment of up to 228 patients."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Multiple Myeloma

A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies (clinicaltrials.gov) - P1; N=67; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

AstraZeneca cans cancer pipeline efforts (FierceBiotech) - “In its fourth-quarter earnings out early Friday morning, U.K.-based Big Pharma AstraZeneca has cut two early-stage experimental meds. The two axed drugs (PDF) are both aimed at cancer targets: The first is MEDI7247, an anti-ASCT2 antibody-drug conjugate, and an oleclumab plus AZD4635 CD73 and A2A inhibitor combo.”

Pipeline update

"$AZN discontinuations: MEDI7247 (anti-ASCT2 ADC) & oleclumab+AZD4635 combo (CD73+A2A inh, relevant to $CRVS )" (@JacobPlieth)

A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: MedImmune LLC; Trial completion date: Mar 2022 ➔ Dec 2019; Trial primary completion date: Mar 2022 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date

A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting; N=336 ➔ 8

Clinical • Enrollment change • Enrollment closed • MSi-H Biomarker

A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies (clinicaltrials.gov) - P1; N=67; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting; N=408 ➔ 67; Trial completion date: Jul 2021 ➔ Feb 2020; Trial primary completion date: Jul 2021 ➔ Feb 2020

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

NEW DRUGS FOR NON‐HODGKIN LYMPHOMA: BEYOND CHEMOTHERAPY: NEW DRUGS FOR OLD TARGETS (ICML 2019) - P1, P1/2, P1a/1b, P1b, P1b/2, P2, P2/3, P3; "...Ofatumumab was approved for patients with chronic lymphocytic leukemia (CLL) at different lines of treatment of this disease, alone or in combination, but failed to demonstrate a benefit and to gain approval in phase 3 studies performed in combination with chemotherapy in relapsed diffuse large B-cell lymphoma (DLBCL) (NCT01014208) or as single agent in patients with relapsed/refractory (R/R) follicular (FL) or other indolent lymphoma (NCT01200589)...In a randomized study comparing bendamustine single agent versus bendamustine combined with obinutuzumab and followed by obinutuzumab maintenance in patients who were assessed as refractory to rituximab, the experimental arm resulted in significant progression free survival (PFS) and overall survival (OS) benefits.6 The GALLLIUM phase 3 study7 demonstrated a significant improvement of PFS in combination with chemotherapy in untreated patients with FL, while no benefit was observed in the

A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=336; Recruiting; Sponsor: MedImmune LLC

Clinical • MSi-H Biomarker • New P1 trial