pasotuxizumab (BAY2010112) / Amgen, Bayer - LARVOL DELTA

Inhibition of the de-ubiquitinse USP30 in human fibroblasts from IPF patients suppresses the fibrotic response (ERS 2024) - "MTX112 at 10 and 30nM significantly (p<0.05) improved mitochondrial function by 50% in IPF fibroblasts. Targeting USP30 may therefore be a novel therapeutic strategy for the treatment of pulmonary fibrosis by improving pulmonary fibroblast mitochondrial function and slowing tissue fibrosis, potentially halting disease progression."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Targeted Protein Degradation

Characterization and root cause analysis of immunogenicity to pasotuxizumab (AMG 212), a prostate-specific membrane antigen-targeting bispecific T-cell engager therapy. (PubMed, Front Immunol) - P1 | "Through a series of stepwise functional assays, our investigation revealed that alongside a more historically immunogenic route of administration, non-tolerant T cell epitopes within the AMG 212 amino acid sequence were likely driving the high-titer, sustained ADA response observed in the SC arm. These mechanistic insights into the AMG 212 ADA response underscore the importance of performing preclinical immunogenicity risk evaluation as well as advocate for continuous iteration to better our biologics."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase I study of pasotuxizumab (AMG 212/BAY 2010112), a PSMA-targeting BiTE (Bispecific T-cell Engager) immune therapy for metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2020) - P1; "Pasotuxizumab had an acceptable safety profile and dose-dependent clinical activity in mCRPC pts. There were two long term responders in the dose escalation. This is the first clinical study showing that a BiTE immune therapy can be efficacious in solid tumors."

IO biomarker • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1 study of pasotuxizumab (BAY 2010112), a PSMA-targeting Bispecific T cell Engager (BiTE) immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2019) - P1; "Pasotuxizumab had an acceptable safety profile and dose-dependent clinical activity in mCRPC pts. There were two long term responders in the dose escalation. This is the first clinical study showing that a BiTE immunotherapy can be efficacious in solid tumors."

IO Biomarker • P1 data

A phase I study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2019) - P1; "A recent trial with pasotuxizumab (AMG 212), a canonical BiTE ® molecule targeting PSMA, demonstrated preliminary antitumor activity in mCRPC...Key inclusion criteria: age ≥18 years; histologically or cytologically confirmed mCRPC refractory to enzalutamide, abiraterone, and/or apalutamide; have failed 1–2 taxane-based regimens or are medically unsuitable for or refuse a taxane regimen; bilateral orchiectomy or on continuous androgen-deprivation therapy; evidence of progressive disease...Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc."

Clinical • P1 data

Phase I study of pasotuxizumab (AMG 212/BAY 2010112), a PSMA-targeting BiTE (Bispecific T-cell Engager) immune therapy for metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2020) - P1; "Pasotuxizumab had an acceptable safety profile and dose-dependent clinical activity in mCRPC pts. There were two long term responders in the dose escalation. This is the first clinical study showing that a BiTE immune therapy can be efficacious in solid tumors."

IO Biomarker • P1 data

"Interesting - didn't Amgen already have a PSMAxCD3 bispecific (AMG 212) or has that one gone by the wayside already?" (@MaverickNY)

Pasotuxizumab, a BiTE immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. (PubMed, Immunotherapy) - P1 | " Data support pasotuxizumab safety in advanced castration-resistant prostate cancer and represent evidence of BiTE monotherapy efficacy in solid tumors. Clinical trial registration: NCT01723475 (ClinicalTrials.gov)."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors. (PubMed) - "Radiolabeled J591 antibody has potential as a targeting agent for solid tumor vasculature and lesion detection. Bone and soft tissue lesions arising from tumors of diverse origin were targeted by the anti-PSMA antibody J591. For the detection of lesions in these tumors by J591 antibody scans, an antibody mass of 20 mg is adequate. The optimal time of imaging is 5 to 7 days post-injection."

Journal • Biosimilar • Oncology

First-in-man Dose Escalation Study of BAY2010112 in Patients With Prostate Cancer (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: Bayer; Trial primary completion date: May 2017 ➔ Aug 2017

Trial primary completion date • Biosimilar • Genito-urinary Cancer • Oncology • Prostate Cancer • Urothelial Cancer

"Pasotuxizumab - no remissions per Recist in first-in-human mCRPC, but recruitment had been halted when $AMGN bought $MITI #GU20" (@JacobPlieth)

Clinical • P1 data

"Will keep my eyes 👀 on AMG 212 (pasotuximab): The monoclonal antibody a promising target prostate-specific membrane antigen (PSMA) to treat #mCRPC @TSchlomm @FabioSchutz78 @cnsternberg @DrChoueiri @Uromigos @GeSRU_de @uroupdate @martin_schostak @declangmurphy" (@amerseburger)

Pasotuxizumab: "AMG 212 antitumor activity (PSA serum level decline) appeared dose dependent, with a mean best change versus baseline of 0.7% (5 μg/day), –17.9% (10 μg/day), –37.4% (20 μg/day), –42.5% (40 μg/day) and –54.9% (80 μg/day)"; Prostate cancer (Amgen) - ASCO 2019

P1 data

Amgen highlights the versatility of the BiTE immuno-oncology platform in multiple tumor types at ASCO 2019 (PRNewswire) - "Updated results from a Phase 1, first-in-human dose-escalation trial of investigational AMG 420...[showed that] AMG 420 induced clinical responses in 13 of 42 patients across the dosing cohorts...The overall response rate at 400 µg/d was 70 percent (7/10). The median duration of response was nine months (range 5.8-13.6 months)...Initial results from a Phase 1 dose-escalation study of investigational AMG 212...[revealed that] PSA decreases of ≥ 50 percent occurred in three patients (n=1 each in 20 µg/d, 40 µg/d and 80 µg/d cohorts). One long-term responder was treated for 14 months (40 µg/d) and one for 19.4 months (80 µg/d)."

P1 data

"Interesting bispecific antibody targeting PSMA and T cells with nice responses observed in mCRPC. #ASCO19 #pasotuxizumab" (@gulleyj1)

Amgen showcases oncology pipeline at ASCO 2019 (Amgen Press Release) - "Amgen...announced that data from its oncology pipeline will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO)...Notable data from the Company's oncology pipeline include first-in-human data for investigational AMG 510...in patients with locally-advanced or metastatic KRASG12C mutant solid tumors...Updated results will also be presented from a Phase 1 dose escalation study evaluating investigational AMG 420....in patients with relapsed or refractory multiple myeloma."

Clinical data

Amgen reports first quarter 2019 financial results (PRNewswire) - "In June 2019, the Company will present the following clinical data at the Annual Meeting of the American Society of Clinical Oncology in Chicago: (i) Updated dose escalation data of AMG 420, a BiTE® (bi-specific T-cell engager) immunotherapy targeting B-cell maturation antigen (BCMA), in patients with relapsed/refractory multiple myeloma; (ii) Dose escalation data of AMG 212, a BiTE® immunotherapy targeting prostate-specific membrane antigen (PSMA), in patients with metastatic castration-resistant prostate cancer."

Clinical data