MEDI0680 / AstraZeneca - LARVOL DELTA

A Randomized Ph2 Study of MEDI0680 in Combination With Durvalumab vs. Nivolumab Monotherapy in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma. (PubMed, Clin Cancer Res) - "MEDI0680 combined with durvalumab was safe and tolerable; however, it did not improve efficacy versus nivolumab monotherapy."

Combination therapy • IO biomarker • Journal • Monotherapy • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • TMB

Results from a randomised phase I/II trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC) (ESMO 2019) - P1/2; "Efficacy was similar with combined M+D and N monotherapy in pts with TKI-pretreated, IO-naïve, metastatic ccRCC, but more pts discontinued M+D due to TRAEs. Clinical trial identification: NCT02118337. Legal entity responsible for the study: AstraZeneca."

Clinical • IO biomarker • P1/2 data • PD(L)-1 Biomarker • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Pharmacokinetics and pharmacodynamics of MEDI0680, a fully human anti-PD-1 monoclonal antibody, in patients with advanced malignancies. (PubMed, Cancer Chemother Pharmacol) - "PK-RO simulations demonstrated that > 90% RO could be maintained in all subjects after a 20-mg/kg dose every 2 weeks (Q2W). Therefore, 20 mg/kg Q2W and an equivalently fixed dose of 1500 mg was recommended for phase 2 studies."

Journal • PK/PD data • Oncology

[VIRTUAL] Prediction and comparison of PD-1 receptor occupancy in the tumor after treatment with immune checkpoint inhibitors (AACR-II 2020) - "This work aims to predict and compare RO in the tumor for several anti-PD-1 therapeutics (nivolumab, pembrolizumab, INCMGA00012 (MGA012), dostarlimab (TSR-042), MEDI0680, sintilimab (IBI308), cemiplimab (REGN2810)) based on the previously developed PBPK/RO model. Developed PBPK/RO model describes biodistribution of antibodies (mAb) within body fluids, detailed transport across endothelial barrier, two-step binding with membrane-bound PD-1 receptor (taking into account target expression level, number of cells expressing target receptor and internalization process), linear and non-linear clearance of mAb (via uptake by endothelium and internalization of mAb:PD-1 complexes, respectively). The proposed PBPK/RO model is able to predict PK of anti-PD-1 mAbs and RO in blood and tumor without the prior fitting of clinical data. Moreover, predictions of PD-1 occupancy in the tumor may be used for informed dose selection or explanation of clinical trial results. This approach can..."

Checkpoint inhibition • IO biomarker • Oncology • PD-1

"indeed, here are the refs: abstract ph1 MEDI0680/AMP-514+durva at ESMO 2016 https://t.co/B5iLNdx6Wo abstract ph1/2 MEDI0680/AMP-514+durva vs nivo in ccRCC at ESMO 2019 (who even noticed the abstract) https://t.co/f0EtQUhYfK" (@BertrandBio)

Clear Cell Renal Cell Carcinoma

Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies. (PubMed, J Immunother Cancer) - P1 | "MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration."

Clinical • IO Biomarker • Journal • P1 data • Genito-urinary Cancer • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Recent advances and challenges of immune checkpoint inhibitors in immunotherapy of non-small cell lung cancer. (PubMed, Int Immunopharmacol) - "This review aims to summarize the recent advances and challenges of ICIs including nivolumab, pembrolizumab, PF-06801591, MEDI0680, atezolizumab, durvalumab, ipilimumab, tremelimumab, and other new PD-1/PD-L1 and CTLA-4 inhibitors in immunotherapy of NSCLC. We hope to provide a better understanding of the mechanisms, clinical research progress and future research directions of NSCLC immunotherapy."

Checkpoint inhibition • Journal • Review • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PD-L1

A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies (clinicaltrials.gov) - P1/2; N=97; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Enrollment closed • IO Biomarker • PD(L)-1 Biomarker • Biosimilar • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Medimmune establishes three-year partnership with the National Cancer Institute to advance oncology research (Medimmune Press Release) - "MedImmune...announced today that it has entered into two umbrella Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI)...that are focused on immunotherapy and tumor targeted therapies for cancer....the two immunotherapy projects will evaluate: Combination activity of four investigational compounds in genetically engineered mouse models; MEDI4736 (PD-L1), MEDI0680 (PD-1), tremelimumab (CTLA-4) and MEDI6469 (mOX40)...Cancer vaccine combinations with three investigational agents in preclinical models; MEDI4736, tremelimumab and MEDI6469 (mOX40)."

Anticipated preclinical • Licensing / partnership • Oncology

AstraZeneca: Q4 & FY 2015 Results (AstraZeneca) - Anticipated top-line data from P1/2 trial (NCT02027961) in combo with dabrafenib/trametinib in metastatic or unresectable melanoma in 2017; Anticipated completion of enrollment of P1 trial (NCT02118337) in combination with MEDI0680 for advanced malignancies in 2017; Anticipated top-line data from P1 trial (NCT02118337) in combination with MEDI0680 in advanced malignancies in 2018

Anticipated enrollment status • Anticipated P1 data • Anticipated P1/2 data • Melanoma • Oncology

Safety/Efficacy of MEDI-551 in Combination With Immunomodulating Therapies in Subjects With Aggressive B-cell Lymphomas (clinicaltrials.gov) - P1/2; N=38; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar

AstraZeneca: Q3 2014 Results (AstraZeneca) - Anticipated presentation of P1 data for advanced malignancies at ASCO (May 29-Jun 2, 2015)

Anticipated P1 data • Oncology

Safety/Efficacy of MEDI-551 in Combination With Immunomodulating Therapies in Subjects With Aggressive B-cell Lymphomas (clinicaltrials.gov) - P1/2; N=39; Recruiting; Sponsor: MedImmune LLC; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

MedImmune strengthens immune-mediated cancer therapy portfolio with acquisition of Amplimmune (AstraZeneca International Press Release) - "AstraZeneca...announced that MedImmune...has entered into a definitive agreement to acquire Amplimmune...acquisition will bolster MedImmune’s oncology pipeline by obtaining multiple early-stage assets for its immune-mediated cancer therapy (IMT-C) portfolio, including AMP-514...with the aim of an investigational new drug (IND) filing before the end of 2013....The proposed transaction is subject to customary regulatory approvals and is expected to close in the third quarter of 2013...Amplimmune has rapidly developed three biologic product candidates: AMP-224 is in Phase 1b trials in cancer; AMP-110 for autoimmune diseases in partnership with Daiichi Sankyo; and AMP-514 for cancer."

Anticipated IND • M&A • Oncology

MedImmune completes acquisition of Amplimmune (AstraZeneca Press Release) - "AstraZeneca...announced that on 4 October MedImmune...completed its acquisition of Amplimmune...the acquisition bolsters MedImmune’s oncology pipeline by obtaining multiple early-stage assets for its immune-mediated cancer therapy (IMT-C) portfolio, including AMP-514...MedImmune acquired 100 per cent of Amplimmune’s shares for an initial consideration of $225 million and deferred consideration of up to $275 million based on reaching predetermined development milestones."

M&A • Oncology

Phase I, open-label study of MEDI0680, an anti-programmed cell death-1 (PD-1) antibody, in combination with MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in patients with advanced malignancies (ASCO 2015) - Presentation time: Saturday, May 30, 8:00 AM - 11:30 AM; Abstract #TPS3087; P1, N=150; NCT02118337; Sponsor: MedImmune LLC; "The primary objectives are to assess safety and tolerability, and determine the maximum tolerated dose of MEDI0680 in combination with MEDI4736. Secondary objectives include assessment of antitumor activity (including objective response rate, disease control rate, duration of response, progression-free survival, and overall survival), pharmacokinetics, and immunogenicity of the combination."

Clinical protocol • Oncology

A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies (clinicaltrials.gov) - P1; N=48; Active, not recruiting; Sponsor: MedImmune LLC; Trial primary completion date: Aug 2017 ➔ Nov 2016

Trial primary completion date • Biosimilar • Melanoma • Oncology • Renal Cell Carcinoma

AstraZeneca: Annual Report 2015 (AstraZeneca) - Discontinuation of MEDI-551 + MEDI0680 in diffuse large B-cell lymphoma due to safety/efficacy reason

Discontinued • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Imfinzi + MEDI0680: Data from P1 trial (NCT02118337) in advanced malignancies and RCC in 2020 or later (AstraZeneca) - Q3 2018 Results

P1 data • Oncology • Renal Cell Carcinoma

A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies (clinicaltrials.gov) - P1; N=58; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed; N=96 ➔ 58

Enrollment change • Trial completion • Biosimilar • Gastrointestinal Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

AstraZeneca: Q3 FY 2016 Results (AstraZeneca) - Anticipated top-line data from P1 trial (NCT02118337) of durvalumab + MEDI0680 in RCC in 2019; Anticipated enrollment completion (expansion) in P1 trial (NCT02013804) in advanced malignancies in Q2 2017; Anticipated top-line data from P1 trial in advanced malignancies in Q4 2016

Anticipated enrollment status • Anticipated P1 data • Oncology

Imfinzi + MEDI0680: Data from P1 trial (NCT02118337) in RCC in 2021 (AstraZeneca) - Q3 FY2017 Results

P1 data • Oncology • Renal Cell Carcinoma

A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies (clinicaltrials.gov) - P1/2; N=97; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Combination therapy • IO Biomarker • Monotherapy • Trial completion • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Despite setback, expert sees novel immunotherapy combos on horizon in mRCC (OncLive) - "Voss: This was a phase I/II clinical trial that was conducted across several institutions in a number of countries. The first portion of the study [evaluated] the safety and tolerability of the combination of MEDI0680, a PD-1–directed monoclonal antibody, with durvalumab, a PD-L1–directed monoclonal antibody."

Interview • P1/2 data

Dr. Voss on phase I/II trial data of MEDI0680/durvalumab versus nivolumab in mRCC (OncLive) - "Martin H. Voss...discusses results of a randomized phase I/II trial (NCT02118337) looking at the combination of MEDI0680 and durvalumab (Imfinzi) versus nivolumab (Opdivo) in metastatic renal cell carcinoma (mRCC)."

P1/2 data • Video