First-in-concept ADC shows promise in head and neck cancer
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
