Methods of Treating Gastrointestinal Cancers and Tumors Thereof Using Combination Therapy

OVERVIEW

This invention relates to a novel combination therapy for treating gastrointestinal cancers and tumors, particularly in patients with mutations in homologous recombination-DNA damage repair (HR-DDR) pathway genes or a family history suggestive of breast or ovarian cancer syndrome. The method involves administering a Poly (ADP ribose) polymerase (PARP) inhibitor in combination with oxaliplatin and an antimetabolite. This approach enhances the sensitivity of gastrointestinal tumor cells to oxaliplatin, thereby improving treatment efficacy and potentially reducing tumor size, halting progression, and inhibiting metastasis. This combination therapy can be particularly effective for patients whose tumors harbor HR-DDR mutations.

BACKGROUND

Gastrointestinal cancers are among the deadliest malignancies, with limited effective treatment options available. Current therapies often struggle to inhibit tumor growth or prevent metastasis. This innovation addresses these challenges by enhancing the effectiveness of existing chemotherapies through the strategic use of PARP inhibitors, which are particularly effective in patients with HR-DDR pathway mutations.

Benefit

• Improves the effectiveness of oxaliplatin by increasing the sensitivity of tumor cells, leading to better clinical outcomes.
• Specifically, benefits patients with HR-DDR mutations, providing a more personalized treatment option.
• Halts tumor growth and reduces the risk of metastasis, potentially increasing progression-free survival.
• Can be used in various stages of treatment, including after prior platinum-based chemotherapy.
• Demonstrates potential in significantly reducing the size of gastrointestinal tumors.

Market Application

• Primarily applied in the treatment of gastrointestinal cancers, including pancreatic, colorectal, and gastric cancers.
• Suitable for personalized treatment plans targeting patients with specific genetic mutations in HR-DDR pathways.
• Can be implemented in clinical settings for patients requiring combination therapy with oxaliplatin.
• Potential for development into a commercially available combination therapy drug, enhancing existing treatment regimens.
• Can be used in ongoing studies to explore the effectiveness of combination therapies in treating various cancer types.

Publications

• A Phase I/II Study of Veliparib (ABT-888) in Combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer. Clin Cancer Res (2020) 26 (19): 5092–5101.
  DOI: 10.1158/1078-0432.CCR-20-1301
• US National Phase filed Pub. No. US 2022/02111657 A1.