lorvotuzumab mertansine (IMGN901) / AbbVie - LARVOL DELTA

Children's Oncology Group's 2023 blueprint for research: Development therapeutics. (PubMed, Pediatr Blood Cancer) - "These trials have included single-agent studies to evaluate agents such as cabozantinib in multi-disease cohorts, to trametinib, larotrectinib, and lorvotuzumab in disease-specific cohorts, as well as the pediatric Molecular Analysis for Therapy Choice (MATCH) study including multiple single agents targeted for biomarker-selected pediatric tumors. The ongoing vision and direction of DVL is to support the disease committees of COG to develop novel agents and combinations to advance the care of children with cancer."

Journal • Oncology • Pediatrics

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. (PubMed, Lung Cancer) - "Antibody-drug conjugates (ADCs) are rapidly establishing their place and have shown promising preliminary data in lung cancer with impressive response rates and survival outcomes in previously treated patients.There are several ADCs currently in clinical trials for NSCLC and small cell lung cancer (SCLC). These ADCs often have different targets which include HER2, HER3, TROP2, CEACAM5, and MET in NSCLC and DLL3 in SCLC.Here we review the safety, and efficacy of newer ADCs in lung cancer including ado-trastuzumab emtansine, trastuzumab deruxetecan, patritomab deruxetecan, datopotamab deruxetecan, sacituzumab govitecan, SAR408701, Telisotuzumab vedotin, rovalpituzumab tesirine, lorvotuzumab mertansine, and sacituzumab govitecan.  Several novel methods are underway to improve the safety and efficacy of ADCs which include increasing the drug to antibody ratio (DAR), the potency of the payload, using more innovative payloads and replacing the antibody."

Journal • Review • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CEACAM5 • DLL3 • ERBB3 • HER-2 • TROP2

Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma (clinicaltrials.gov) - P2; N=62; Completed; Sponsor: Children's Oncology Group; Active, not recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Sep 2021

Clinical • Trial completion • Trial completion date • Brain Cancer • Nephrology • Neuroblastoma • Neurofibrosarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • Wilms Tumor • MRI • NCAM1

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. (PubMed, Antibodies (Basel)) - "Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted."

Clinical • Journal • Review • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

Safety Study Using Weekly Infusions of BB-10901 in Patients With Small Cell Lung Cancer (clinicaltrials.gov) - P1/2; N=64; Completed; Sponsor: ImmunoGen, Inc.; Recruiting ➔ Completed

Clinical • Trial completion • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • NCAM1

ADVL1522: A phase 2 study of lorvotuzumab mertansine (IMGN901) in children with relapsed or refractory wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor, or synovial sarcoma-A Children's Oncology Group study. (PubMed, Cancer) - "Lorvotuzumab mertansine (110 mg/m ) is tolerated in children at the adult recommended phase 2 dose; clinical activity is limited."

Clinical • Journal • P2 data • Diabetes • Neuroblastoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Wilms Tumor

Phase I study of lorvotuzumab mertansine (LM, IMGN901) in combination with lenalidomide (Len) and dexamethasone (Dex) in patients with CD56-positive relapsed or relapsed/refractory multiple myeloma (MM) (ASH 2012) - Presentation time: Monday, December 10, 2012: 4:45 PM; Abstract #728; P1, N=44; NCT00991562; "During dose escalation, 1 patient experienced Grade 4 neutropenia and hyperuricemia...Grade 1–2 PN occurred in 8 patients (42%) and grade 3 PN was observed only in 1 pt in the dose-expansion cohort. Two patients developed grade 3 tumor lysis syndrome (TLS)"

P1 data • Multiple Myeloma • Oncology

Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma. (PubMed) - Am J Blood Res - "We demonstrate that multi-drug resistance protein-1 (MDR-1) was upregulated in MM cells grown in contact with stroma, likely responsible for the observed resistance. This study emphasizes the importance of incorporating the elements of tumor microenvironment during preclinical testing of novel therapeutics."

Journal • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

Management of Multiple Myeloma with Second-Generation Antibody-Drug Conjugates. (PubMed) - BioDrugs - "Lorvotuzumab mertansine, indatuximab ravtansine, and milatuzumab-doxorubicin are currently under clinical development for use in multiple myeloma (MM). Preliminary data from recent studies indicate that these agents induce responses in patients with relapsed and/or refractory MM and have an acceptable safety profile."

Journal • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma. (PubMed, Clin Lymphoma Myeloma Leuk) - "This completed phase I trial of single-agent lorvotuzumab mertansine provides ample evidence of safety and signals of clinical activity for this agent, warranting its further clinical development as part of combination regimens for the management of MM."

Clinical • Journal • P1 data • PK/PD data

An Open-label Phase II Study of Lorvotuzumab Mertansine (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting; Initiation date: Sep 2015 ➔ May 2015; Trial primary completion date: Sep 2017 ➔ May 2017

Clinical • Enrollment open • Trial initiation date • Trial primary completion date

An Open-label Phase II Study of Lorvotuzumab Mertansine (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

An Open-label Phase II Study of Lorvotuzumab Mertansine (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: M.D. Anderson Cancer Center; Trial primary completion date: May 2017 ➔ May 2018

Clinical • Trial primary completion date

An Open-label Phase II Study of Lorvotuzumab Mertansine (clinicaltrials.gov) - P2; N=9; Completed; Sponsor: M.D. Anderson Cancer Center; Active, not recruiting ➔ Completed; N=60 ➔ 9; Trial primary completion date: May 2018 ➔ Jun 2017

Clinical • Enrollment change • Trial completion • Trial primary completion date

An Open-label Phase II Study of Lorvotuzumab Mertansine (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

Clinical • New P2 trial

NCAM1/FGF module serves as a putative pleuropulmonary blastoma therapeutic target. (PubMed, Oncogenesis) - "Targeting the progenitor blastoma and these transitions with an anti-NCAM1 immunoconjugate (Lorvotuzumab mertansine) inhibited tumor growth and progression providing new paradigms for PPB therapeutics. Altogether, our novel in-vivo PPB xenograft model allowed us to enrich for highly proliferating stem-like cells and to identify FGFR and NCAM1 as two key players that can serve as therapeutic targets in this poorly understood and aggressive disease."

Journal

Advances in antibody therapeutics targeting small-cell lung cancer. (PubMed, Adv Clin Exp Med) - "...Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials. It was demonstrated that chemotherapy in combination with bevacizumab can improve the progression-free survival (PFS) in phase III trials. The insulin-like growth factor-1 receptor (IGF-1R) is associated with a poor prognosis in SCLC, while the anti-IGF-1R monoclonal antibody figitumumab has a potential therapeutic value. Tarextumab, an antibody that blocks both Notch2 and Notch3 signaling, in combination with etoposide and platinum (EP) in patients with untreated extensive-stage SCLC, proved to be well-tolerated and showed dosedependent anti-tumor activity. The therapeutic effect of sacituzumab govitecan, BW-2 and lorvotuzumab mertansine in SCLC warranted further evaluation. Bec2/BCG as an adjuvant vaccination in patients with limited-disease SCLC..."

Journal • Review

Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma (clinicaltrials.gov) - P2; N=62; Active, not recruiting; Sponsor: Children's Oncology Group; N=114 ➔ 62

Clinical • Enrollment change

Role of investigational monoclonal antibodies in the treatment of multiple myeloma: A systematic review. (ASCO 2019) - "...Isatuximab (anti-CD38) and F50067 (anti-CXCR4) were the only MoAbs which produced encouraging results as monotherapy with ORR of 66.7% and 32% respectively. Isatuximab use in combination with Len-Dex produced CBR of 83%, and in combination with pomalidomide and dexamethasone CBR of 73%... CD38 remains an important target for further clinical trials in combination therapy. Trials using indatuximab, pembrolizumab, lorvotuzumab, siltuximab, and dacetuzumab in combination therapy produced better outcomes as compared to monotherapies. Surface receptor targeting antibodies in relapsed refractory multiple myeloma."

Review

Emerging immune targets for the treatment of multiple myeloma. (PubMed, Immunotherapy) - "...Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising."

Journal