Asco 2021 – Merus intrigues in pancreatic cancer

Merus has managed to do what many others have not: show activity in pancreatic cancer. It did this by looking specifically at a genetic mutation: its lead bispecific, zenocutuzumab, produced a 40% overall response rate among 10 pancreatic patients with NRG1 fusions, an Asco abstract revealed. However, performance in other cancer types was less impressive. The analysis, of the phase 1/2 Enrgy trial plus an early-access programme, also included 18 patients with NSCLC and five with other solid tumours; across all 33 the ORR was 27% at a January 12 data cut-off. Merus, whose stock fell 5% this morning, will hope that the pancreatic result holds up – and perhaps for an improvement in other tumour types – when updated results are presented at Asco on June 4. The NRG1 fusion niche is small, with only around 1% of solid tumours thought to carry this mutation, but not many others are currently looking at this space. Merus’s main rival is Elevation Oncology, which is developing seribantumab, an asset Merrimack abandoned after its failure in NSCLC. Boehringer’s approved NSCLC drug Gilotrif has also shown evidence of a benefit in NRG1 fusion-positive patients, and is being investigated in the Asco-sponsored Tapur umbrella trial.

Selected projects targeting NRG1 fusion mutations
Company Project Description Cancer type(s) Status
Merus Zenocutuzumab (MCLA-128) Her2/Her3-targeting bispecific Pancreatic, NSCLC, other solid tumours Ph1/2 Enrgy & early access programme presented at Asco 2021
Elevation Oncology Seribantumab (MM-121) Anti-Her3 monoclonal antibody Various solid tumours inc. pancreatic & lung Ph2 Crestone completes Jun 2022
Rain Therapeutics Tarloxotinib  Pan-ErbB inhibitor NSCLC & other solid tumours Ph2 completed Mar 2021; project appears to be deprioritised
Boehringer Ingelheim Gilotrif Pan-ErbB inhibitor Approved for EGFR-mutated NSCLC Asco-sponsored Tapur includes Gilotrif/NRG1 arm
Hummingbird Bioscience HMBD-001 Anti-Her3 monoclonal antibody Various solid tumours  Preclinical
Source: Evaluate Pharma &

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