Shots:

• John spoke about the results from the P-II MOUNTAINEER Trial evaluating its lead candidate in mCRPC
• He also talked about TUKYSA (tucatinib) in combination with trastuzumab as a potential treatment for mCRPC
• The interview gives a deeper understanding of Seagen’s vision of developing transformative cancer treatment options

Smriti: Share the details (ROA, MOA & formulations) of TUKYSA. 

John Strickler: Tukysa (tucatinib) is an oral tyrosine kinase inhibitor with high selectivity for HER2.  

Smriti: Please explain the study design of the P-II MOUNTAINEER trial. 

John Strickler: This study consisted of three cohorts. Cohort A has launched years ago and the preliminary results of that cohort were shown at the ESMO World Congress in 2019. Based on the promising activity demonstrated in that cohort, the study was further expanded. Patients were randomized to Cohort B, which was the tucatinib/trastuzumab combination, or tucatinib monotherapy. Patients who had not responded to tucatinib monotherapy were allowed to cross over to the combination.

Smriti: What are the key upshots from the data presented at the ESMO? 

John Strickler: In chemotherapy-refractory patients with HER2+ RAS wild-type metastatic colorectal cancer, tucatinib in combination with trastuzumab demonstrated durable and clinically meaningful antitumor activity. The confirmed response rate was 38% with a median duration of response of 12.4 months and a median PFS of 8.2 months. Overall, the regimen was very well tolerated. There were no treatment-related deaths.

Smriti: What are your next steps for the further clinical trials of Tukysa? 

John Strickler: These results provide a rationale for continued investigation of tucatinib in combination with trastuzumab in first-line treatment of HER2-positive mCRC.  MOUNTAINEER-03 is a phase 3 trial evaluating tucatinib in combination with trastuzumab and mFOLFOX6 versus standard of care treatment in first-line HER2+ mCRC.  

Smriti: How common is HER2 in mCRC? 

John Strickler: Up to 3% of patients with mCRC and approximately 10% with RAS/BRAF wild-type tumors have HER2 amplification or overexpression. TUKYSA is highly selective for HER2, which allows complete blockade of HER2 signaling without some of the side effects that occur due to off-target activity.

Smriti: How does this regimen help address the unmet needs of patients living with HER2+ mCRC? 

John Strickler: There are currently no approved therapies for patients with HER2+ RAS wild-type mCRC. Tucatinib in combination with trastuzumab has the potential to become a new standard of care for this patient population. Patients with HER2+ mCRC who progress on early lines of chemotherapy regimens receive limited clinical benefit from current standard-of-care treatments. The non-chemotherapeutic approach offers patients the opportunity to receive meaningful clinical benefits without the toxicity of traditional cytotoxic chemotherapy.  

*John Strickler is the principal investigator of the MOUNTAINEER trial

Source: Canva

About the Author:

John Strickler is the Associate Professor of Medicine at Duke University School of Medicine where he is Co-Leader of the Molecular Tumor Board and Associate Director of Clinical Research, GI Oncology. John specializes in the treatment of gastrointestinal (GI) cancers with a focus on clinical trials. He earned his bachelor's degree in Economics and political science from the University of North Carolina and MD from The University of Chicago Pritzker School of Medicine.

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