Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (37302522)
Authors Weng W, Meng T, Pu J, Ma L, Shen Y, Wang Z, Pan R, Wang M, Chen C, Wang L, Zhang J, Zhou B, Shao S, Qian Y, Liu SH, Hu W, Meng X
Title AMT-562, a novel HER3-targeting antibody drug conjugate, demonstrates a potential to broaden therapeutic opportunities for HER3-expressing tumors.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 2023 Jun 11 Mol Cancer Ther
URL
Abstract Text HER3 is a unique member of the epidermal growth factor receptor family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting ADC molecule with clinical efficacy in non-small cell lung cancer (NSCLC). However, over 60% of patients are non-responsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected due to its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid (PDX/PDO) models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS and TKI showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetics and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402-insensitive tumors.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AMT-562 AMT-562 10 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
AMT-562 AMT 562|AMT562 HER3 (ERBB3) Antibody 30 AMT-562 is an antibody drug conjugate (ADC) comprising an ERBB3 (HER3) antibody conjugated to exatecan, which potentially inhibits tumor growth (PMID: 37302522).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E ERBB3 pos colon cancer sensitive AMT-562 + LY2603618 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Rabusertiv (LY2603618) and AMT-562 synergistically inhibited tumor growth in a cell line xenograft model of ERBB3 (HER3)-positive colon cancer harboring BRAF V600E (PMID: 37302522). 37302522
ERBB3 positive esophagus squamous cell carcinoma sensitive AMT-562 Preclinical - Pdx Actionable In a preclinical study, AMT-562 inhibited tumor growth in a patient-derived xenograft (PDX) model of ERBB3 (HER3)-positive esophageal squamous cell carcinoma (PMID: 37302522). 37302522
BRAF V487_P492delinsA ERBB3 pos pancreatic cancer sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited growth in a cell line xenograft model of ERBB3 (HER3)-positive pancreatic cancer harboring BRAF V487_P492delinsA (PMID: 37302522). 37302522
BRAF V600E ERBB3 pos colon cancer sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited tumor growth in a cell line xenograft model of ERBB3 (HER3)-positive colon cancer harboring BRAF V600E (PMID: 37302522): 37302522
ERBB3 positive gastroesophageal junction adenocarcinoma sensitive AMT-562 Preclinical - Pdx Actionable In a preclinical study, AMT-562 inhibited tumor growth in a patient-derived xenograft (PDX) model of ERBB3 (HER3)-positive gastroesophageal junction adenocarcinoma (PMID: 37302522). 37302522
ERBB3 positive colon cancer sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited tumor growth in a cell line xenograft model of ERBB3 (HER3)-positive colon cancer with a complete response in 4 of 5 mice and inhibited growth in patient-derived organoids in culture (PMID: 37302522). 37302522
ERBB3 positive lung non-small cell carcinoma sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited tumor growth in a cell line xenograft model of ERBB3 (HER3)-positive non-small cell lung cancer (PMID: 37302522). 37302522
ERBB3 positive breast cancer predicted - sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited tumor growth in a cell line xenograft model of low ERBB3 (HER3)-expressing breast cancer (PMID: 37302522). 37302522
ERBB3 positive stomach cancer sensitive AMT-562 Preclinical - Cell line xenograft Actionable In a preclinical study, AMT-562 inhibited tumor growth in a cell line xenograft model of ERBB3 (HER3)-positive gastric cancer (PMID: 37302522). 37302522
ERBB3 positive esophagus adenocarcinoma sensitive AMT-562 Preclinical - Pdx Actionable In a preclinical study, AMT-562 inhibited tumor growth in a patient-derived xenograft (PDX) model of ERBB3 (HER3)-positive esophageal adenocarcinoma (PMID: 37302522). 37302522
ERBB3 amp rectum cancer sensitive AMT-562 Preclinical - Pdx Actionable In a preclinical study, AMT-562 inhibited tumor growth in a patient-derived xenograft (PDX) model of ERBB3 (HER3)-amplified rectal cancer (PMID: 37302522). 37302522