solitomab (AMG 110) / Amgen - LARVOL DELTA

Mice humanized for the immune system as validated tool for therapeutic antibody development (AACR 2025) - "We developed the human A375 melanoma model in huCD34+ NCG mice to evaluate the combination strategy of relatlimab (anti-LAG-3 antibody) and nivolumab (anti-PD-1 antibody) approved at the beginning of 2024 as a first-line treatment for specific melanoma indications...We also developed huPBMC mice that exhibit exclusively T-cell lineage and are suitable option to evaluate T-cell engagers like the CD3xEpCAM bispecific antibody, solitomab...Mice humanized for the immune system exhibiting either multiple lineages (CD34+ huNCG) or just T-cell lineage (huPBMC) proved themselves suitable tools to assess non-mouse cross-reactive anti-tumor immunotherapy assets. Expertise in handling such models and deep knowledge in their benefits and limitations are required to selecting the most valuable model to perform preclinical studies predictive of human therapeutic response."

Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD34

Genome-wide association study and genomic selection of spike-related traits in bread wheat. (PubMed, Theor Appl Genet) - "Additionally, the eight stable and major MTAs, including MTA259, MTA64, MTA66, MTA94, MTA110, MTA165, MTA180, and MTA164, were converted into cost-effective and efficient detection markers. This study provided valuable genetic resources and reliable molecular markers for wheat breeding programs."

Journal

Automated 42 PDX 3D in vitro tumor models of the TME screen immuno-oncology and targeted compounds and biologics for antitumor effects and MOA (AACR 2024) - "The panel has been tested against chemotherapy drug cisplatin and the immunotherapy biologic, Solitomab, an EpCAM/CD3 bispecific antibody. In addition, immune cells and supernatant in the IO assay can be recovered from the wells and used for flow cytometry profiling and cytokine assays. In summary, the novel 42-PDX panel described here offers a unique and powerful tool for rapidly generating preclinical data and a better understanding the drug activity at the pharmacology stages, opening the door for faster and more human relevant drug discovery for cancer patients."

Immuno-oncology • Preclinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Novel Hydrogel-Based 3D In Vitro Tumor Panel of 30 PDX Models Incorporates Tumor, Stromal and Immune Cell Compartments of the TME for the Screening of Oncology and Immuno-Therapies. (PubMed, Cells) - "We screened the panel first against the chemotherapy drug Cisplatin to demonstrate feasibility and robustness, and subsequently assayed immuno-oncology agents Solitomab (CD3/EpCAM bispecific T-cell engager) and the immune checkpoint inhibitors (ICIs) Atezolizumab (anti-PDL1), Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA4). The described 30-model panel represents a significant advancement toward screening in vitro models of the tumor microenvironment that include tumor, fibroblast, and immune cell populations in an extracellular matrix hydrogel, with robust and standardized high content image analysis in a planar hydrogel. The platform is aimed at rapidly screening various combinations and novel agents and forming a critical conduit to the clinic, thus accelerating drug discovery for the next generation of therapeutics."

Immune cell • Journal • Preclinical • Stroma • Immune Modulation • Immunology • Oncology

Novel Fab-peptide-HLA-I fusion proteins for redirecting pre-existing anti-CMV T cell immunity to selective eliminate carcinoma cells. (PubMed, Oncoimmunology) - "In contrast, analogous treatment with equimolar amounts of EpCAM/CD3-directed bispecific T-cell engager solitomab resulted in a massive release of IFNγ, a feature commonly associated with adverse cytokine-release syndrome. Combinatorial treatment with EpCAM-ReTARG and EGFR-ReTARG strongly potentiated selective cancer cell elimination owing to the concerted action of the corresponding cognate anti-CMV CD8 T cell clones. In conclusion, ReTARG fusion proteins may be useful as an alternative or complementary form of targeted cancer immunotherapy for 'cold' solid cancers."

Journal • Cytomegalovirus Infection • Infectious Disease • Oncology • Solid Tumor • B2M • CD8 • EGFR • EPCAM • IFNG

Studies on a new antimicrobial peptide from Vibrio proteolyticus MT110. (PubMed, Prep Biochem Biotechnol) - "The physicochemical properties and stability in wide pH and temperature ranges showed the potential of peptide-MT110 for its development as a drug candidate. This is believed to be the first report on an AMP from Vibrio proteolyticus."

Journal • Infectious Disease

A Clinically Validated pH-Sensitive Nanomedicine Platform for Encapsulating Therapeutic Bispecific T cell engagers for Tumor Specific Delivery and Activation (SITC 2022) - "Methods A panel of BsAbs (including biosimilar equivalents of blinatumomab, solitomab, and others) was used to demonstrate encapsulation by the ON-BOARD platform and pH-dependent activation. Further pH-specific cell killing was confirmed by TDCC assays in multiple in vitro models including Burkitt lymphoma, breast cancer, colorectal cancer, and lung cancer. Conclusions The ON-BOARD pH-sensitive nanoparticle platform demonstrated potential as an effective and universal tool for solid tumor specific activation and delivery of bispecific antibody therapeutics, potentially minimizing systemic side effects."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Breast Cancer • Burkitt Lymphoma • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • HER2 Breast Cancer • Leukemia • Lung Cancer • Lymphoma • Oncology • Solid Tumor • CD19 • CD20 • CEACAM5 • EPCAM • HER-2

A 30 PDX Panel of 3D in vitro tumor models identifies responders to Pembrolizumab and Solitomab. (SITC 2022) - "Endpoints including tumor size and killing highlighted PDX responders to both Pembrolizumab and Solitomab. These data highlight the ability to screen various immunotherapy compounds in a standardized 3D PDX in vitro panel for determining antitumor effect in drug discovery and translational research to enhance patient outcomes."

IO biomarker • Preclinical • Gastrointestinal Cancer • Kidney Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CASP3 • CASP7

EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab. (PubMed, J Thorac Dis) - "Different concentrations of nanoparticle albumin-bound paclitaxel (Nab-PTX) and cisplatin were used to treat the two groups of cells and compare their drug resistance. Further, EC Eca109 cell spheres have a high expression level of EpCAM, and EpCAM may be one of the markers of EC stem cells. Therefore, EpCAM could be used as a potential molecular target of immunotherapy for EC, and solitomab may become an effective immunotherapeutic drug for chemotherapy-resistant EC cells."

IO biomarker • Journal • Esophageal Cancer • Gastrointestinal Cancer • Oncology • EPCAM

[VIRTUAL] HPN601 is a protease-activated EpCAM-targeting T cell engager with an improved safety profile for the treatment of solid tumors (SITC 2020) - "For example, clinical testing of solitomab, an EpCAM-targeting T cell engager, resulted in severe dose-limiting toxicities, including elevated liver transaminases, hyperbilirubinemia, and diarrhea. Conclusions HPN601 is a conditionally active EpCAM-targeting T cell engager with a ten-fold improved therapeutic window compared to a constitutively active EpCAM-targeting T cell engager. An EpCAM-specific T cell engager with an improved safety profile could address unmet needs in many solid tumors and demonstrate the feasibility of using conditionally active T cell engagers to target more solid tumor antigens."

Clinical • Oncology • Solid Tumor • EPCAM • IFNG • IL10 • IL2 • IL6

[VIRTUAL] HPN601 is a protease-activated EpCAM-targeting T cell engager with an improved safety profile for the treatment of solid tumors (SITC 2020) - "For example, clinical testing of solitomab, an EpCAM-targeting T cell engager, resulted in severe dose-limiting toxicities, including elevated liver transaminases, hyperbilirubinemia, and diarrhea. Conclusions HPN601 is a conditionally active EpCAM-targeting T cell engager with a ten-fold improved therapeutic window compared to a constitutively active EpCAM-targeting T cell engager. An EpCAM-specific T cell engager with an improved safety profile could address unmet needs in many solid tumors and demonstrate the feasibility of using conditionally active T cell engagers to target more solid tumor antigens."

Clinical • Oncology • Solid Tumor • EPCAM • IFNG • IL10 • IL2 • IL6

PNOC015: MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov) - P1/2; N=24; Active, not recruiting; Sponsor: Sabine Mueller, MD, PhD; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

PNOC015: MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov) - P1/2; N=24; Active, not recruiting; Sponsor: Sabine Mueller, MD, PhD; Trial completion date: Sep 2021 ➔ Mar 2025; Trial primary completion date: Sep 2020 ➔ Mar 2025

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

TIM-3 blockade combined with bispecific antibody MT110 enhances the anti-tumor effect of γδ T cells. (PubMed, Cancer Immunol Immunother) - "By reinvigorating dysfunctional γδ T cells and promoting them to accumulate at tumor sites, the combined use of TIM-3 inhibitor and MT110 could further enhance the anti-tumor effect of the adoptively transfused γδ T cells. These results may have clinical implications for the design of new translational anti-tumor regimens aimed at combining checkpoint blockade and immune cell redirection."

Journal • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor

[VIRTUAL] Eradication of EpCAM expressing solid tumors by low-affinity CAR T cells (AACR-II 2020) - "However, clinical trials with anti-EpCAM antibodies (ING-1, 3622W94) and bispecific T cell engager antibodies (Solitomab) have shown significant dose-limiting toxicities, resulting in very limited clinical responses... Low-affinity EpCAM targeting CAR T cells demonstrated durable antitumor activity against various tumor models in vivo. To enhance safety and therapeutic efficacy, micromolar affinity anti-EpCAM CAR T cells are currently being evaluated to limit cell killing to EpCAM-positive tumor cells while sparing normal cells with basal levels of EpCAM expression."

CAR T-Cell Therapy • Brain Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CSF2 • EPCAM • IFNG • IL2

Immunotargeting and therapy of cancer by advanced multivalence antibody scaffolds. (PubMed, J Drug Target) - "Novel multivalent Ab scaffolds (e.g., MDX-447, MT110, CD20Bi, TF2, and FBTA05) and mimetic Abs (e.g., Adnectin, DARPins, Ecallantide) offer improved pharmacokinetic and pharmacodynamic properties. Here, we discuss the avidity and multivalency and provide comprehensive insights into advanced Ab scaffolds used for immunotargeting and therapy of cancer."

Journal • Oncology

Impact of Diverse Immune Evasion Mechanisms of Cancer Cells on T Cells Engaged by EpCAM/CD3-Bispecific Antibody Construct AMG 110. (PubMed) - "Our data suggest that diverse mechanisms employed by cancer cells to fend off T cells cannot inactivate AMG 110-engaged T cells, and that inhibitory effects observed in vitro may be overcome by increased concentrations of the BiTE® antibody construct."

Journal • Biosimilar • Oncology

Selective inhibition of IDO1, D-1-methyl-tryptophan (D-1MT), effectively increased EpCAM/CD3-bispecific BiTE antibody MT110 efficacy against IDO1(hi)breast cancer via enhancing immune cells activity. (PubMed, Int Immunopharmacol) - "In vivo assay, combination of D-1MT with MT110 in NOD/SCID mice bearing IDO(hi) MCF-7 xenografts or MuS110 in immune competent BALB/c mice bearing IDO(hi) 4T1 xenografts suggested the similar synergistic effect. Together, IDO inhibition could reverse the suppression of T cells due to IDO expressing on breast cancer, and improve the antitumor efficacy of EpCAM/CD3-bispecific BiTE antibody."

Journal • Biosimilar • Breast Cancer • Gene Therapies • Oncology • Solid Tumor

High-dose MTX110 (soluble panobinostat) safely administered into the fourth ventricle in a nonhuman primate model. (PubMed, J Neurosurg Pediatr) - "MTX110 can be safely infused into the fourth ventricle in nonhuman primates at supratherapeutic doses. Postinfusion CSF panobinostat levels peak immediately in the fourth ventricle and then rapidly decrease over 24 hours. Panobinostat is detectable at low levels in CSF measured from the lumbar cistern up to 4 hours after infusions. These results will provide background data for a pilot clinical trial in patients with recurrent medulloblastoma."

Journal

Biodistribution of a CD3/EpCAM bispecific T-cell engager is driven by the CD3 arm. (PubMed, J Nucl Med) - "PET images and ex-vivo biodistribution in immunocompetent mice with 89Zr-muS110, targeting mouse CD3 (Kd = 2.9 nM) and mouse EpCAM (Kd = 21 nM), and 89Zr-hyS110, targeting only mouse CD3 (Kd = 2.9 nM), showed uptake in tumor, spleen and other lymphoid organs, while the human-specific control BiTE 89Zr-AMG 110 showed similar tumor uptake but lacked spleen uptake. Significance: 89Zr-muS110 biodistribution is mainly dependent on the T-cell targeting arm with limited contribution of its second arm, targeting EpCAM. These findings highlight the need for extensive biodistribution studies of novel bispecific constructs as results might have implications for their respective drug development and clinical translation."

Journal

Infusion of Panobinostat (MTX110) Into the Fourth Ventricle or Tumor Resection Cavity in Children and Adults With Recurrent Medulloblastoma (clinicaltrials.gov) - P1; N=5; Not yet recruiting; Sponsor: The University of Texas Health Science Center, Houston

Clinical • New P1 trial • Brain Cancer • CNS Tumor • Embryonal Tumor • Medulloblastoma • Oncology • Solid Tumor • MRI

Infusion of Panobinostat (MTX110) Into the Fourth Ventricle in Children and Adults With Recurrent Medulloblastoma (clinicaltrials.gov) - P1; N=5; Recruiting; Sponsor: The University of Texas Health Science Center, Houston; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Brain Cancer • CNS Tumor • Embryonal Tumor • Medulloblastoma • Oncology • Solid Tumor

CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas (clinicaltrials.gov) - P1; N=9; Recruiting; Sponsor: Stergios Zacharoulis

Clinical • New P1 trial

Infusion of Panobinostat (MTX110) Into the Fourth Ventricle or Tumor Resection Cavity in Children and Adults With Recurrent Medulloblastoma (clinicaltrials.gov) - P1; N=5; Not yet recruiting; Sponsor: The University of Texas Health Science Center, Houston

Clinical • New P1 trial • MRI

PNOC015: MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: Sabine Mueller, MD, PhD; Suspended ➔ Recruiting

Enrollment open