cergutuzumab amunaleukin (RG7813) / Roche - LARVOL DELTA

Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors. (PubMed, ESMO Open) - "Consistent with its mechanism of action, CA had a manageable safety profile and expanded immune effector cells but not Treg. Further development in combination with additional immunomodulatory agents is warranted."

First-in-human • Journal • P1 data • PK/PD data • Fatigue • Genito-urinary Cancer • Hematological Disorders • Hypotension • Melanoma • Oncology • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Thrombocytopenia • CD8 • CEACAM5 • IL2 • IL2RA

Biomarkers of activity from a phase I study of cergutuzumab amunaleukin in patients with advanced solid tumors. (PubMed, J Immunother Cancer) - P1 | "CA-induced immune pharmacodynamic effects in peripheral blood and in the tumor microenvironment without preferential Treg cell activation in patients with metastatic/unresectable CEA+ solid tumors."

Biomarker • First-in-human • Journal • P1 data • Oncology • Solid Tumor • CD14 • CD8 • CEACAM5 • IL2 • IL2RA • PD-L1 • TNFA

Cergutuzumab Amunaleukin in Combination with Atezolizumab in Patients with Carcinoembryonic Antigen-Positive Advanced/Metastatic Solid Tumors. (PubMed, Clin Cancer Res) - P1b | "The safety profile of this combination was manageable. Prominent pharmacodynamic effects were elucidated; antitumor activity was limited."

Journal • Oncology • Solid Tumor • CEACAM5 • CRP • IL2 • IL2RA

Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors. (PubMed, Clin Cancer Res) - "These preliminary findings suggest that obinutuzumab pretreatment before CEA-IL2v administration in patients with CEA+ solid tumors may be a feasible and potent ADA mitigation strategy, with an acceptable safety profile, supporting broader investigation of obinutuzumab pretreatment for ADA mitigation in other settings."

Journal • Hepatology • Oncology • Solid Tumor • CEACAM5

A humanized minipig model for the toxicological testing of therapeutic recombinant antibodies. (PubMed, Nat Biomed Eng) - "In line with observations in human patients, the genetically modified minipigs tolerated the clinically non-immunogenic IgG1κ-isotype monoclonal antibodies daratumumab and bevacizumab, and elicited antibodies against the checkpoint inhibitor atezolizumab and the engineered interleukin cergutuzumab amunaleukin. The humanized minipigs can facilitate the safety and efficacy testing of therapeutic antibodies."

Journal • Oncology • IGH

A humanized minipig model for the toxicological testing of therapeutic recombinant antibodies (Nature) - "Here we report the generation of Göttingen minipigs carrying a mini-repertoire of human genes for the immunoglobulin heavy chains γ1 and γ4 and the immunoglobulin light chain κ. In line with observations in human patients, the genetically modified minipigs tolerated the clinically non-immunogenic IgG1κ-isotype monoclonal antibodies daratumumab and bevacizumab, and elicited antibodies against the checkpoint inhibitor atezolizumab and the engineered interleukin cergutuzumab amunaleukin. The humanized minipigs can facilitate the safety and efficacy testing of therapeutic antibodies."

Preclinical • Oncology

89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation in a dose-dependent manner and role of IL-2 receptor-binding (ESMO 2016) - P1; "CEA-IL2v (cergutuzumab amunaleukin, RG7813) is an engineered IL-2 variant (IL-2v) antibody directed against Carcinoembryonic Antigen (CEA) with abolished IL-2 receptor (IL-2R) &agr; (CD25) binding. At all doses, 89Zr- CEA-IL-2v accumulated in spleen and secondary lymphoid tissues, due to IL-2R mediated uptake. CEA-mediated tumor accumulation was observed in a dose-dependent manner with consistent targeting starting at 20 mg CEA-IL2v; a phase I study as monotherapy and with atezolizumab is ongoing."

Clinical • Biosimilar • Oncology

A Study of RO6895882 in Patients With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Hoffmann-La Roche; Trial primary completion date: Aug 2016 ->Sep 2015

Trial primary completion date • Biosimilar • Colorectal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology

A Study of Intravenous (IV) Cergutuzumab Amunaleukin and Atezolizumab in Combination in Participants With Locally Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1b; N=70; Completed; Sponsor: Hoffmann-La Roche; Active, not recruiting ➔ Completed

Clinical • Trial completion

Prediction of the optimal dosing regimen using a mathematical model of tumour uptake for immunocytokine-based cancer immunotherapy. (PubMed, Clin Cancer Res) - "The model presented here allows simulation of individualized treatment plans for optimal dosing and scheduling of immunocytokines for anti-cancer immunotherapy."

Journal

A Study of Intravenous (IV) Cergutuzumab Amunaleukin and Atezolizumab in Combination in Participants With Locally Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1b; N=70; Active, not recruiting; Sponsor: Hoffmann-La Roche; Recruiting ➔ Active, not recruiting; Trial completion date: May 2019 ➔ Oct 2019; Trial primary completion date: May 2019 ➔ Oct 2019

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

A novel PD1-IL2v immunocytokine for preferential cis-activation of IL-2R signaling on PD-1 expressing T cell subsets strongly potentiates anti-tumor T cell activity of PD-1 checkpoint inhibition and IL-2R-beta-gamma agonism (AACR 2019) - "...We have described tumor-targeted CEA-IL2v and FAP-IL2v immunocytokines that are based on an engineered IL2v moiety with abolished binding to IL-2Ra (CD25) to avoid undesired CD25-mediated toxicities and Treg expansion...In summary, our data demonstrate that preferential cis-targeting of IL2v to PD-1+ antigen specific T cells with PD1-IL2v results in a strong potentiation of T cell response and anti-tumor efficacy as compared to the combination of PD-1 checkpoint inhibition with FAP-IL2v. These preclinical data establish PD1-IL2v as a promising next generation IL-2 for cancer immunotherapy."

Checkpoint inhibition