NCT04750954

Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors

A Phase 1b Trial of M3814 (Peposertib) in Combination With Lutetium 177 Dotatate for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial is to find out the best dose, possible benefits and/or side effects of peposertib when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell formation, so as to help block the formation of growths that may become cancer. Radioactive drugs, such as lutetium Lu 177 dotatate, may deliver radiation directly to tumor cells and not harm normal cells. Adding peposertib to lutetium Lu 177 dotatate may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and to determine the recommended phase 2 dose (RP2D) of lutetium Lu 177 dotatate in combination with M3814 (peposertib). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 4, 8, and 12 months post-therapy. III. To measure duration of response (DOR) associated with the combination. IV. To evaluate progression-free survival (PFS). CORRELATIVE OBJECTIVES: I. Measure the somatostatin receptor uptake on gallium 68 dotatate or Copper 64 dotatate at baseline. II. Perform lutetium Lu 177 dotatate dosimetry. III. Determine the pharmacokinetic (PK) parameters of M3814 (peposertib). IV. Describe the tumor molecular profile using whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq) and correlate it with treatment outcome. V. Collect plasma for circulating tumor deoxyribonucleic acid (DNA) (ctDNA) assessment. VI. Collect blood for biobanking and future correlative studies. VII. Measure association of overall response rate with gallium 68 dotatate-positron emission tomography (PET)/computed tomography (CT) or Copper 64 dotatate measurements and Krenning score. OUTLINE: This is a dose-escalation study of peposertib followed by a dose-expansion study. Patients receive peposertib orally (PO) once daily (QD) or twice daily (BID) on days 1-21 and lutetium Lu 177 dotatate intravenously (IV) over 30 minutes on day 1. Treatment repeats every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/magnetic resonance imaging (MRI) throughout the trial and undergo collection of blood samples on study. After completion of study treatment, patients are followed up every 4 months for 24 months.

Conditions

• Neuroendocrine Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Lutetium Lu 177 Dotatate	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Peposertib	Given PO

Timeline

• Start date: 2021-07-22
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2021-02-11
• Last updated: 2026-04-17

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study