Pyxis Oncology has announced positive preliminary data from its ongoing Phase I clinical studies evaluating micvotabart pelidotin (MICVO) in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).  

MICVO is an antibody-drug conjugate (ADC) targeting extradomain-B of fibronectin (EDB+FN), a non-cellular structural component of the tumour extracellular matrix (ECM). 

The update includes preliminary data from both the Phase I monotherapy study in 2L+ R/M HNSCC and the Phase I/II study evaluating MICVO in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, pembrolizumab, in 1L/2L+ R/M HNSCC. 

Dr Glenn Hanna, Director, Center for Cancer Therapeutic Innovation and Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School, said: “As we look ahead to where the treatment landscape may include next-generation EGFR combination therapies as first-line options for select patients, many will still lack effective treatments, particularly in later lines – which remains a significant unmet clinical need. MICVO monotherapy presents an intriguing potential option for these later-line patients, while the initial data in combination with pembrolizumab also shows promising potential synergies in first-line patients.” 

Key findings

Monotherapy  

The ongoing Phase I monotherapy study is a two-part study: Part I was a dose escalation study across multiple doses and tumour types, with initial data shared in November 2024, with Part 2, a dose expansion cohort at 5.4mg/kg in 2L+ R/M HNSCC, currently ongoing. 

  • 18 patients were treated at 5.4 mg/kg; intravenous (IV) dosed every three weeks (Q3W). 
  • Confirmed overall response rate (ORR) of 46% (6/13), including one complete response by RECIST v1.1. 
  • Disease control rate (DCR) of 92%. 
  • Generally well tolerated, with no Grade 4 ADC payload treatment-related adverse events (TRAEs) of interest observed. No Grade 5 events occurred. 

Combination therapy  

The ongoing Phase I/II study evaluating MICVO in combination with KEYTRUDA is currently in dose escalation across multiple doses and tumour types, including 1L/2L+ R/M HNSCC.  

  • Seven patients were treated in total, four at 3.6mg/kg and three at 4.4mg/kg of MICVO, plus fixed dose 200mg of pembrolizumab; IV Q3W.  
  • Confirmed ORR of 71%. 
  • DCR of 100%. 
  • Generally well tolerated, with no Grade 3 or Grade 4 ADC payload TRAEs of interest observed. No Grade 5 events occurred. 

Diana Turner, Deputy Editor, DDW