NCT06161493

ZEN003694 Combined With Niraparib in Patients With Metastatic or Recurrent Solid Tumors

Phase l Study of a BET Inhibitor, ZEN003694, Combined With a PARP Inhibitor, Niraparib in Patients With Metastatic or Recurrent Solid Tumors

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Haider Mahdi · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase I, open label, dose determining study of oral niraparib in combination with ZEN003694 given daily in 28-day cycles will enroll patients with metastatic or recurrent solid cancer. Dose escalation will follow the mTPI-2/Keyboard design. Eligible patients will receive therapy until disease progression or unacceptable toxicities are experienced.

Detailed description

PARPis impair the repair of single strand DNA breaks leading to double strand DNA breaks especially in patients with defects in the HR pathway. PARP is have been extensively studied in ovarian cancer and are approved for patients with germline or somatic BRCA mutant ovarian cancer after 2-3 lines of chemotherapy. PARPis have been also approved as maintenance therapy in first line and recurrent ovarian cancer after partial or complete response to platinum-based therapy. PARPis have prominent activity in BRCA mutated cancer with lower activity in the BRCA wild type HRD negative ovarian cancer. Approximately 18-24% of ovarian cancer harbor somatic or germline BRCA mutation and 50% harbor alteration in the homologous recombination (HR) pathway. Further, PARPi therapy is frequently associated with PARPi resistance. Therefore, there is a need to reverse PARPi resistance and enhance response to PARPi in PARPi resistant ovarian cancer. Recently, significant pre-clinical evidence has shown that BETi's synergize with PARPi's through downregulation of the transcription of several HR genes. It is hypothesized that BETi may suppress HR and enhance non-homologous end joining thereby sensitizing HR-proficient cancer cells to PARP inhibition, and also BETi has been described to reverse PARPi resistance. To test this hypothesis, this Phase I trial will test the combination of niraparib and ZEN003694 in recurrent or metastatic solid cancers.

Conditions

• Ovarian Cancer
• Recurrent Solid Tumors

Interventions

Type	Name	Description
DRUG	ZEN003694	A bromodomain extra-terminal inhibitor (BETi) that blocks a group of proteins called bromodomain and extra-terminal (BET), which may counteract the effect of NSD3 on tumor growth.
DRUG	Niraparib	An anti-cancer medication (PARP inhibitor) used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer .

Timeline

• Start date: 2024-01-23
• Primary completion: 2026-12-31
• Completion: 2029-12-31
• First posted: 2023-12-08
• Last updated: 2024-10-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study