NCT05034627

Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer

A Phase I, Open-Label, Dose Finding Study of Calaspargase Pegol-Mnkl in Combination With Cobimetinib in Locally-Advanced or Metastatic Pancreatic Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of calaspargase pegol-mknl in combination with cobimetinib in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Cobimetinib attacks a protein called MEK that has been known to stimulate cells that promote the growth of cancer cells in the body. Calaspargase pegol-mknl is an enzyme that converts the amino acid L-asparagine into aspartic acid and ammonia. Many types of cancer cell rely on the amino acid L-asparagine, and depleting this amino acid with calaspargase pegol-mknl starves cancer cells of this nutrient. Attacking the MEK protein with cobimetinib is thought to further prevent cancer cells from using this amino acid, causing them to die. Giving calaspargase pegol-mknl in combination with cobimetinib may help control the disease in patients with pancreatic cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of calaspargase pegol-mknl in combination with cobimetinib. SECONDARY OBJECTIVES: I. To assess the safety of calaspargase pegol-mknl in combination with cobimetinib. II. To assess preliminary response to treatment with calaspargase pegol-mknl and cobimetinib. III. To monitor levels of plasma asparaginase. EXPLORATORY OBJECTIVE: I. To evaluate therapy induced changes in the tumor and tumor ecosystem. OUTLINE: This is a dose-escalation study. Patients receive calaspargase pegol-mknl intravenously (IV) over 1 hour on day 1 and cobimetinib orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo a biopsy before cycle 1, day1 and again on cycle 2 day 15 per the investiagator's discretion, with an additional biopsy at the time of disease progression. After completion of study intervention, patients are followed up at 3 and 6 months.

Conditions

• Locally Advanced Pancreatic Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma
• Stage II Pancreatic Cancer AJCC v8
• Stage IIA Pancreatic Cancer AJCC v8
• Stage IIB Pancreatic Cancer AJCC v8
• Stage III Pancreatic Cancer AJCC v8
• Stage IV Pancreatic Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
DRUG	Calaspargase Pegol-mknl	Given IV
DRUG	Cobimetinib	Given PO

Timeline

• Start date: 2022-08-09
• Primary completion: 2025-12-16
• Completion: 2026-10-01
• First posted: 2021-09-05
• Last updated: 2025-11-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study