Revolutionizing Treatment for Rare Head and Neck Cancer: PHASE ONE Funds Breakthrough Study for NOTCH-Activated Adenoid Cystic Carcinoma

PHASE ONE Foundation has awarded a $273,768 Medical Grant to Dr. Glenn J. Hanna at Dana-Farber Cancer Institute to support a Phase I/II study in NOTCH-activated Adenoid Cystic Carcinoma (ACC), a rare cancer primarily affecting the salivary glands in the head and neck. 

ACC poses significant treatment challenges due to its rarity, high rates of distant metastasis, and limited effective options for advanced cases. 

While initially manageable through surgery and radiation, nearly half of ACC patients eventually face metastasis, and current treatments, including chemotherapy and immunotherapy, have shown limited clinical benefits, emphasizing the necessity of new therapeutic strategies for this difficult-to-treat cancer. 

Dr. Hanna’s Phase I/II trial investigates the effects of CB-103, an oral pan-Notch inhibitor, in combination with other therapies for patients with NOTCH pathway mutations– a mutation frequently observed in aggressive ACC cases and linked to shorter relapse-free periods and poor survival rates. 

"PHASE ONE Foundation’s support provides critical funds to ensure our patients with aggressive ACC have access to a novel therapy that aims to improve outcomes.” –Dr. Glenn J. Hanna, Director of the Center for Cancer Therapeutic Innovation and Head and Neck Oncologist at Dana-Farber Cancer Institute, and Associate Professor of Medicine at Harvard Medical School. 

Preclinical data suggests synergy between Notch and CDK4/6 signaling. Building on this, Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, known for its ability to block the formation of new blood vessels, has been included in the study based on evidence suggesting that it may counter ACC’s ability to foster tumor growth. 

By exploring the combination of CB-103 with Abemaciclib or Lenvatinib and Abemaciclib alone, Dr. Hanna aims to leverage the potential synergies among these therapies, which could lead to improved treatment responses and progression-free survival rates. 

PHASE ONE supports research that moves promising discoveries from the lab to the clinic. By funding Dr. Hanna's study, the organization reinforces its mission to find breakthrough therapies for rare and aggressive cancers and address the critical needs in cancer care. 

“Investing in high-potential research is at the core of what we do. We believe in empowering the brightest minds in cancer research to develop transformative therapies. Dr. Hanna's work exemplifies our mission to support pioneering studies that have the potential to change the trajectory for patients dealing with dire prognoses.” –Marc Lebowitz, PHASE ONE Granting Co-Chair 

As this research unfolds, it serves as a beacon of hope for patients and families impacted by NOTCH-activated ACC, potentially leading to new, effective treatment regimens and ultimately improving survival rates.