Strategies for clinical dose optimization of T cell-engaging therapies in oncology

Mechanistically Modeling Peripheral Cytokine Dynamics Following Bispecific Dosing in Solid Tumors

(2023) Jared Weddell   CPT-Pharmacometrics & Systems Pharmacology

Translational findings for odronextamab: From preclinical research to a first‐in‐human study in patients with CD20+ B‐cell malignancies

(2022) Min Zhu et al.   CTS-Clinical and Translational Science

Safety and preliminary clinical activity of JNJ-63898081 (JNJ-081), a PSMA and CD3 bispecific antibody, for the treatment of metastatic castrate-resistant prostate cancer (mCRPC).

(2022) Emerson A. Lim et al.   JOURNAL OF CLINICAL ONCOLOGY

Dissecting the mechanism of cytokine release induced by T-cell engagers highlights the contribution of neutrophils

(2022) Gabrielle Leclercq et al.   OncoImmunology

Novel Bi-Specific Immuno-Modulatory Tribodies Potentiate T Cell Activation and Increase Anti-Tumor Efficacy

(2022) Margherita Passariello et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Phase I Study of Safety, Tolerability, and Efficacy of Tebentafusp Using a Step-Up Dosing Regimen and Expansion in Patients With Metastatic Uveal Melanoma

(2022) Richard D. Carvajal et al.   JOURNAL OF CLINICAL ONCOLOGY

Physiologically Based Modeling to Predict Monoclonal Antibody Pharmacokinetics in Humans from in vitro Physiochemical Properties

(2022) Shihao Hu et al.   mAbs

Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology

(2022) Yanchen Zhou et al.   Journal for ImmunoTherapy of Cancer

Quantitative Clinical Pharmacology of CAR T‐Cell Therapy

(2022) Sarah A. Holstein et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Mosunetuzumab: First Approval

(2022) Connie Kang   DRUGS

Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated efficacy and safety results from MajesTEC-1.

(2022) Ajay K. Nooka et al.   JOURNAL OF CLINICAL ONCOLOGY

Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated results from MonumenTAL-1.

(2022) Monique C. Minnema et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase 2 study of tarlatamab, a DLL3-targeting, half life–extended, bispecific T-cell engager (HLE BiTE)immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC).

(2022) Suresh S. Ramalingam et al.   JOURNAL OF CLINICAL ONCOLOGY

Teclistamab in Relapsed or Refractory Multiple Myeloma

(2022) Philippe Moreau et al.   NEW ENGLAND JOURNAL OF MEDICINE

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma

(2022) Suzette Girgis et al.   Targeted Oncology

Quantitative systems pharmacology modeling sheds light into the dose response relationship of a trispecific T cell engager in multiple myeloma

(2022) R. E. Abrams et al.   Scientific Reports

Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma

(2022) Tomoki Yoneyama et al.   PLoS Computational Biology

Preclinical InVivo Data Integrated in a Modeling Network Informs a Refined Clinical Strategy for a CD3 T-Cell Bispecific in Combination with Anti-PD-L1

(2022) Javier Sánchez et al.   AAPS Journal

A Probody® T-cell-engaging bispecific antibody targeting EGFR and CD3 inhibits colon cancer growth with limited toxicity

(2022) Leila M. Boustany et al.   CANCER RESEARCH

Semimechanistic Physiologically‐Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B‐Cell Lymphomas

(2022) Tommy Li et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Factors Affecting the Cancer Immunotherapeutic Efficacy of T Cell Bispecific Antibodies and Strategies for Improvement

(2022) Meixiao Long et al.   IMMUNOLOGICAL INVESTIGATIONS

Development of T-cell engagers selective for cells co-expressing two antigens

(2022) Danielle M. Dicara et al.   mAbs

Considerations for design, manufacture, and delivery for effective and safe T-cell engager therapies

(2022) Tara Arvedson et al.   CURRENT OPINION IN BIOTECHNOLOGY

Overcoming the challenges associated with CD3+ T-cell redirection in cancer

(2021) Ajit Singh et al.   BRITISH JOURNAL OF CANCER

Immune cell engagers in solid tumors: promises and challenges of the next generation immunotherapy

(2021) G. Fucà et al.   ESMO Open

A Two-Pore Physiologically Based Pharmacokinetic Model to Predict Subcutaneously Administered Different-Size Antibody/Antibody Fragments

(2021) Zhe Li et al.   AAPS Journal

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

(2021) Zheng Tian et al.   Journal of Hematology & Oncology

The Association Between Glucocorticoid Administration and the Risk of Impaired Efficacy of Axicabtagene Ciloleucel Treatment: A Systematic Review

(2021) Zhen Sun et al.   Frontiers in Immunology

Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas

(2021) Ross Salvaris et al.   Journal of Personalized Medicine

Promising tolerability and efficacy results from dose-escalation in an ongoing phase Ib/II study of mosunetuzumab (M) with polatuzumab vedotin (Pola) in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (B-NHL).

(2021) L Elizabeth Budde et al.   JOURNAL OF CLINICAL ONCOLOGY

Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).

(2021) Amrita Y. Krishnan et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase I/II, multicenter, open-label study of REGN5668 (mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab (programmed death [PD]-1 Ab) or REGN4018 (MUC16 x CD3 bsAb) in recurrent ovarian cancer (rOVCA).

(2021) Ira Seth Winer et al.   JOURNAL OF CLINICAL ONCOLOGY

Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).

(2021) Jesus G. Berdeja et al.   JOURNAL OF CLINICAL ONCOLOGY

Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study

(2021) Saad Z Usmani et al.   LANCET

Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning

(2021) Lauric Haber et al.   Scientific Reports

Bispecific Antibodies: A Smart Arsenal for Cancer Immunotherapies

(2021) Gihoon You et al.   Vaccines

A Novel Approach for Quantifying the Pharmacological Activity of T-Cell Engagers Utilizing In Vitro Time Course Experiments and Streamlined Data Analysis

(2021) Arthur Van De Vyver et al.   AAPS Journal

Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study

(2021) Suzanne Trudel et al.   BLOOD

Safety and Anti-Tumor Activity of Plamotamab (XmAb13676), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Subjects with Relapsed/Refractory Non-Hodgkin's Lymphoma

(2021) Krish Patel et al.   BLOOD

Subcutaneous (SC) Administration of Mosunetuzumab with Cycle 1 Step-up Dosing Is Tolerable and Active in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphomas (R/R B-NHL): Initial Results from a Phase I/II Study

(2021) Nancy L. Bartlett et al.   BLOOD

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study

(2021) Lihua E. Budde et al.   JOURNAL OF CLINICAL ONCOLOGY

Novel in Vivo and in Vitro Pharmacokinetic/Pharmacodynamic-Based Human Starting Dose Selection for Glofitamab

(2021) Nicolas Frances et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

The Drug-Dosing Conundrum in Oncology — When Less Is More

(2021) Mirat Shah et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy

(2021) Tara Arvedson et al.   Annual Review of Cancer Biology-Series

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma

(2021) Ann-Marie E. Bröske et al.   Blood Advances

Recent advances and challenges of bispecific antibodies in solid tumors

(2021) Yuze Wu et al.   Experimental Hematology & Oncology

Clinical Activity of REGN1979, a Bispecific Human, Anti-CD20 x Anti-CD3 Antibody, in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL)

(2020) Rajat Bannerji et al.   BLOOD

Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 2, immune checkpoint inhibitor antibodies

(2020) Aude Desnoyer et al.   EUROPEAN JOURNAL OF CANCER

Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics

(2020) Cris Kamperschroer et al.   Journal of Immunotoxicology

Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia

(2020) Shuangyou Liu et al.   Blood Cancer Journal

Predicting bioavailability of monoclonal antibodies after subcutaneous administration: Open innovation challenge

(2020) Manuel Sánchez-Félix et al.   ADVANCED DRUG DELIVERY REVIEWS

The BiTE (Bispecific T‐Cell engager) platform: Development and future potential of a targeted immuno‐oncology therapy across tumor types

(2020) Hermann Einsele et al.   CANCER

Development of a minimal physiologically-based pharmacokinetic/pharmacodynamic model to characterize target cell depletion and cytokine release for T cell-redirecting bispecific agents in humans

(2020) Xiling Jiang et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Perspective: Designing T-Cell Engagers With Better Therapeutic Windows

(2020) Omid Vafa et al.   Frontiers in Oncology

A Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor

(2020) Huilin Ma et al.   AAPS Journal

Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology

(2020) Alison Betts et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation–Updated Consensus and Review 2020

(2020) Vibha Jawa et al.   Frontiers in Immunology

Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma

(2020) Mark R. Middleton et al.   CLINICAL CANCER RESEARCH

Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model

(2020) Huilin Ma et al.   Journal for ImmunoTherapy of Cancer

Mitigating the risk of cytokine release syndrome in a Phase I trial of CD20/CD3 bispecific antibody mosunetuzumab in NHL: impact of translational system modeling

(2020) Iraj Hosseini et al.   npj Systems Biology and Applications

Predicting tumor killing and T-cell activation by T-Cell Bispecific antibodies as a function of target expression: combining in vitro experiments with systems modeling

(2020) Arthur J Van De Vyver et al.   MOLECULAR CANCER THERAPEUTICS

Combination of T-Cell Bispecific Antibodies With PD-L1 Checkpoint Inhibition Elicits Superior Anti-Tumor Activity

(2020) Johannes Sam et al.   Frontiers in Oncology

Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies

(2019) Nathan D. Trinklein et al.   mAbs

A Translational Quantitative Systems Pharmacology Model for CD3 Bispecific Molecules: Application to Quantify T Cell-Mediated Tumor Cell Killing by P-Cadherin LP DART®

(2019) Alison Betts et al.   AAPS Journal

A review of bispecific antibodies and antibody constructs in oncology and clinical challenges

(2019) Frans V. Suurs et al.   PHARMACOLOGY & THERAPEUTICS

A Modeling Framework to Characterize Cytokine Release upon T‐Cell–Engaging Bispecific Antibody Treatment: Methodology and Opportunities

(2019) Xiaoying Chen et al.   CTS-Clinical and Translational Science

Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy

(2019) Christina Claus et al.   Science Translational Medicine

Modelling of the Time-Varying Pharmacokinetics of Therapeutic Monoclonal Antibodies: A Literature Review

(2019) Antoine Petitcollin et al.   CLINICAL PHARMACOKINETICS

CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity

(2019) Ji Li et al.   Science Translational Medicine

Exposure-Response Analyses Indicate a Promising Benefit/Risk Profile of Mosunetuzumab in Relapsed and Refractory Non-Hodgkin Lymphoma

(2019) Chi-Chung Li et al.   BLOOD

Integrated Pharmacokinetic/Pharmacodynamic Model of a Bispecific CD3xCD123 DART Molecule in Nonhuman Primates: Evaluation of Activity and Impact of Immunogenicity

(2018) Olivia Campagne et al.   CLINICAL CANCER RESEARCH

Tumor-Shed Antigen Affects Antibody Tumor Targeting: Comparison of Two 89Zr-Labeled Antibodies Directed against Shed or Nonshed Antigens

(2018) Jae-Ho Lee et al.   Contrast Media & Molecular Imaging

Development of a Target cell-Biologics-Effector cell (TBE) complex-based cell killing model to characterize target cell depletion by T cell redirecting bispecific agents

(2018) Xiling Jiang et al.   mAbs

Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach

(2018) Alison Betts et al.   mAbs

Relative Target Affinities of T-Cell–Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model

(2018) Danielle Mandikian et al.   MOLECULAR CANCER THERAPEUTICS

Cytokine release syndrome

(2018) Alexander Shimabukuro-Vornhagen et al.   Journal for ImmunoTherapy of Cancer

Rationale for Combining Bispecific T Cell Activating Antibodies With Checkpoint Blockade for Cancer Therapy

(2018) Sebastian Kobold et al.   Frontiers in Oncology

Bifunctional PD-1 × αCD3 × αCD33 fusion protein reverses adaptive immune escape in acute myeloid leukemia

(2018) Monika Herrmann et al.   BLOOD

Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety

(2018) Diego Ellerman   METHODS

Perspectives on Subcutaneous Route of Administration as an Immunogenicity Risk Factor for Therapeutic Proteins

(2017) Lora Hamuro et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL

(2017) J Duell et al.   LEUKEMIA

An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection

(2017) Haleh Saber et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

Mechanistic Projection of First-in-Human Dose for Bispecific Immunomodulatory P-Cadherin LP-DART: An Integrated PK/PD Modeling Approach

(2016) X Chen et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Application of a MABEL Approach for a T-Cell-Bispecific Monoclonal Antibody

(2016) Sherri Dudal et al.   JOURNAL OF IMMUNOTHERAPY

A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

(2016) S Hipp et al.   LEUKEMIA

CEA TCB: A novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors

(2016) Marina Bacac et al.   OncoImmunology

Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies

(2016) Marco Ruella et al.   Computational and Structural Biotechnology Journal

Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer

(2015) Julia Stieglmaier et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Immune Escape Mechanisms as a Guide for Cancer Immunotherapy

(2014) G. L. Beatty et al.   CLINICAL CANCER RESEARCH

IgG Subclasses and Allotypes: From Structure to Effector Functions

(2014) Gestur Vidarsson et al.   Frontiers in Immunology

Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML

(2013) G. S. Laszlo et al.   BLOOD

Disease–Drug–Drug Interaction Involving Tocilizumab and Simvastatin in Patients With Rheumatoid Arthritis

(2011) C Schmitt et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Effects of Charge on Antibody Tissue Distribution and Pharmacokinetics

(2010) C. Andrew Boswell et al.   BIOCONJUGATE CHEMISTRY

Target-mediated drug disposition model for drugs that bind to more than one target

(2010) Leonid Gibiansky et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Gaining insights into the consequences of target-mediated drug disposition of monoclonal antibodies using quasi-steady-state approximations

(2009) Hans Peter Grimm   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Factors determining antibody distribution in tumors

(2008) G THURBER et al.   TRENDS IN PHARMACOLOGICAL SCIENCES