Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer

NCT06736717 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00161071
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer is a deadly disease and will be the second leading cause of cancer related death behind lung cancer by 2030. Over 62,000 people are diagnosed each year in the United States with about 90% succumbing to the disease within 5 years. In the metastatic setting, NALIRIFOX, FOLFIRINOX and nab-paclitaxel-gemcitabine are standard treatment options in patients with good performance status (Eastern Cooperative Oncology Group \[ECOG\] 0/1). All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/FOLFIRINOX and 8.7 months for nab-paclitaxel-gemcitabine versus 6.7 months for gemcitabine alone. There is an urgent need to improve treatment of patients with current and emerging therapeutic strategies. KRAS is the most common oncogene mutated in pancreatic adenocarcinoma, and it is mutated in nearly all tumors. Mutant KRAS is essential for PDAC growth, where the constitutive activated RAS proteins contribute to tumorigenesis, treatment resistance, and metastases. Despite research and drug development efforts focused on KRAS, no effective RAS inhibitors have been approved for the treatment of pancreatic cancer with KRAS mutation. The poor prognosis of KRAS-mutated PDAC patients and the absence of KRAS-targeted therapies, highlight the urgency to develop novel therapies aimed at KRAS. This study will investigate onvansertib (also known as PCM-075 and NMS-1286937) as the first PLK1-specific adenosine triphosphate competitive inhibitor administered by oral route to enter clinical trials with proven antitumor activity in different preclinical models.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Imaging RECIST 1.1

  Approximately 2 years

Secondary Outcomes (5)

• Adverse Events

  2 years

• Anti-tumor activity by Disease Control Rate (DCR)

  8 weeks

• Anti-tumor activity by Duration of Response (DOR)

  2 years

• Progression Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Study Drug: Onvansertib: Orally daily on D1 - 5 of each 14-day cycle NALIRIFOX Intravenous D1 of each 14-day cycle

Drug: Onvansertib; Drug: NALIRIFOX

Interventions

Onvansertib DRUG

20 or30mg flat dose - depending on results from safety lead-in. Administered concurrently with NALIRIFOX. Once daily on D1-5 of each 14-day cycle.

Also known as: PCM-075, NMS-1286937

Treatment

NALIRIFOX DRUG

Chemotherapy regimen of nanoliposomal irinotecan, oxaliplatin, fluorouracil \[5-FU\], and leucovorin. Intravenously on Day 1 of each 14-day cycle.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability of participant to understand this study, and participant willingness to sign a written informed consent. Remote consenting will be allowed on a case-by-case basis, but will not replace in-person visits for labs/physical, etc.
• Males and females age ≥ 18 years
• ECOG Performance Status 0 - 1
• Measurable disease by RECIST 1.1
• Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
• Locally advanced unresectable or metastatic disease who are treatment naive
• No previous systemic therapy in the metastatic setting
• Participant must be willing to submit archival tissue if available and sufficient - otherwise fresh biopsy collection will be performed at screening UNLESS it is deemed medically unsafe for the participant. If participant does not have archival tissue and is not able to undergo a fresh biopsy at this time, enrollment will be per the principal investigator's discretion
• Adequate organ function, defined as follows:
• Leukocytes (White Blood Cell \[WBC\]) \> 3 K/UL
• Absolute Neutrophil Count \>1.5K/UL
• Platelets \>100K/UL
• Hemoglobin ≥ 9 g/dL(level must be maintained without transfusions)
• Calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation
• Total bilirubin ≤ 1.5 x ULN

You may not qualify if:

• Simultaneously enrolled in any therapeutic clinical trial
• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Is pregnant or breastfeeding
• Has a known allergic reaction to any excipient contained in the study drug formulation
• Active Grade 3 (per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.027) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
• Patient has had major surgery within 4 weeks prior to enrollment
• Untreated or symptomatic brain metastasis
• Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (e.g., intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)
• Unable or unwilling to swallow study drug
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure (CHF) Class II or higher according to the New York Heart Association (NYHA) Functional Classification, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection
• Known active infection with HIV, with measurable viral titer, and/or active infection with hepatitis B or C (patients who have had a hepatitis B virus immunization are eligible)
• Known active infection with SARS-CoV-2 where symptoms are present
• Clinically significant ascites or pleural effusions
• Patients with a history of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix or prostate, or other solid tumors curatively treated with no evidence of disease for \> 2 years

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Cardiff Oncology: collaborator

Study Sites (1)

The University of Kansas Cancer Center, Westwood Campus

Kansas City, Kansas, 66205, United States

RECRUITING

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  BACKGROUND

Related Links

• UpToDate. Causes of long QT syndrome

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

onvansertib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Anup Kasi, MD, MPH

  The University of Kansas Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

KUCC Navigation

CONTACT

913-945-7552; ctnursenav@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: December 17, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)