Summary of Key Points

Diagnosis and Progression

• Initial Diagnosis: Diagnosed with stage 4 pancreatic neuroendocrine tumors (pNETs) in June 2017, characterized by:
  • Liver metastases
  • Ki-67 of 8% (Grade 2, well-differentiated)
• Current Stage: By October 2023, the condition progressed to:
  • Poorly differentiated pancreatic neuroendocrine carcinoma (pNEC)
  • Ki-67 > 70% (Grade 3), indicating a more aggressive cancer form
  • Noted dedifferentiation aligns with known tendencies of NETs to escalate in aggressiveness over time

Treatment History

• Therapies Administered:
  • Chemotherapy
  • Peptide receptor radionuclide therapy (PRRT)
  • Immunotherapy (Opdivo [nivolumab] and Yervoy [ipilimumab])
• Response and Complications:
  • Remarkable improvement noted by mid-August 2024
  • Development of complications including:
    • Immunotherapy-induced colitis
    • Suspected pneumonitis or bacterial pneumonia
    • Episodes of hypoxemia (oxygen saturation levels fluctuating between 88–90%, falling to 82% in emergency situations)

DLL3 Status and Trial Disqualification

• Tumor Characteristics:
  • Tumor cells express DLL3
• Trial Disqualification: Disqualified from DAREON-5 trial (testing BI 764532, a DLL3/CD3 bispecific T-cell engager) due to:
  • Insufficient DLL3 expression (<50%)
  • DLL3 as a potential therapeutic target in neuroendocrine carcinomas, with notable expression in 54.8% of gastroenteropancreatic NECs, commonly associated with aggressive subtypes

Current Needs

• Clinical Trials: Seeking phase 2 or later clinical trials utilizing immunotherapy drugs targeting DLL3 to manage or reduce progression of pNEC, taking into consideration:
  • Medical history, including prior colitis and current respiratory issues
• Doctor Search: Looking for medical professionals with experience in treating similar diagnoses.