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

February 3, 2025 updated by: University of Kansas Medical Center

A Phase 1b/2 Trial of Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Kansas
      • Kansas City, Kansas, United States, 66205
        • Recruiting
        • The University of Kansas Cancer Center, Westwood Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • If known Gilbert's syndrome then discuss with principal investigator. Email documentation of discussion and approval will be saved and documented for source.
  • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
  • Women of child-bearing potential (WOCBP) and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section.

Exclusion Criteria:

  • 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
  • Any active disease condition that would render the protocol treatment dangerous or impair the ability of the patient to receive study drug per PI discretion.
  • Any condition (e.g., psychological, geographical, etc.) that does not permit compliance with the protocol
  • Treatment with any of the drugs listed in section with title; Prohibited or Restricted Concomitant Medications at the time of study treatment initiation. Planned concomitant use of medications known to prolong the QT/QTc interval according to institutional guidelines. Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers. Patients currently receiving these agents who can be switched to alternate therapy are not excluded. Inhibitors should be stopped at least 1 week prior to the first dose of protocol therapy and inducers should be stopped at least 2 weeks prior to initiation of protocol therapy

  • QT interval: Fridericia's correction (QTcF) > 470 milliseconds.

    • A single ECG is sufficient. Triplicate may be done per PI discretion. If triplicate ECG completed, the QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation that are readily corrected (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility
    • Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

Study Drug: Onvansertib:

Orally daily on D1 - 5 of each 14-day cycle

NALIRIFOX Intravenous D1 of each 14-day cycle
Drug: Onvansertib

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.

Other Names:
  • NMS-1286937
  • PCM-075
Drug: NALIRIFOX

Chemotherapy regimen of nanoliposomal irinotecan, oxaliplatin, fluorouracil [5-FU], and leucovorin.

Intravenously on Day 1 of each 14-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Approximately 2 years
Imaging RECIST 1.1
Approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 2 years
The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.025
2 years
Anti-tumor activity by Disease Control Rate (DCR)
Time Frame: 8 weeks
Calculated as the percentage of participants that achieve any of the following at 8 weeks: complete response, partial response, or stable disease, as defined by RECIST v1.1.
8 weeks
Anti-tumor activity by Duration of Response (DOR)
Time Frame: 2 years
Calculated as the average length of time between response to treatment and disease progression, defined per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
2 years
Progression Free Survival (PFS)
Time Frame: 2 years
The duration of time from start of treatment until objective tumor progression or death, as determined by medical record imaging
2 years
Overall Survival (OS)
Time Frame: 2 years
Duration of time from start of treatment to death, determined by medical record
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Kansas Medical Center

Collaborators

Cardiff Oncology

Investigators

  • Principal Investigator: Anup Kasi, MD, MPH, The University of Kansas Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2025

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

November 20, 2024

First Submitted That Met QC Criteria

December 13, 2024

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 3, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00161071

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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