A Study of Narmafotinib Given in Combination With Modified FOLFIRINOX in Patients With Metastatic Pancreatic Cancer

NCT07026279 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AMP945-PC-202U1111-1298-5990
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 2

Brief Summary

This study is testing narmafotinib, a type of drug called a focal adhesion kinase (FAK) inhibitor, when it is given in combination with 4 chemotherapy drugs in a regimen called FOLFIRINOX, to patients who have pancreatic cancer which has metastasised (spread). The study is being run in 2 parts. Part A will test increasing dose levels of narmafotinib in at least 3 people per dose at up to 4 dose levels to assess safety. Part B will test 2 of the dose levels from Part A in 20 people per dose, to select the best dose to take forward into future studies. Participants will take narmafotinib as oral capsules every day. They will also receive mFOLFIRINOX chemotherapy on Day 1 and and Day 15 of 28-day cycles.

Conditions

Pancreatic Cancer Metastatic

Keywords

pancreatic cancer; PDAC; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study

  TEAEs during study treatment and follow up periods

  From first dose of study drug to end of study, an expected average of 6 months

• Part B: identification of optimal dose of narmafotinib

  The optimal dose will be selected based on a review of safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and any other available relevant data

  From first dose of study drug to end of study, an expected average of 6 months

Secondary Outcomes (9)

• narmafotinib levels in plasma

  Days -7, -6, -1, 1 and 15 of Run-In/Cycle 1; and Day 1 of Cycles 2 and 4 (each cycle is 28 days)

• narmafotinib levels in plasma

  Days -7, -6, -1, 1 and 15 of Run-In/Cycle 1; and Day 1 of Cycles 2 and 4 (each cycle is 28 days)

• narmafotinib levels in plasma

  Days -7, -6, -1, 1 and 15 of Run-In/Cycle 1; and Day 1 of Cycles 2 and 4 (each cycle is 28 days)

• Overall response rate (ORR)

  Imaging every 56 days per participant, with an expected average duration of 6 months

• Overall survival (OS)

  Imaging every 56 days per participant, with an expected average duration of 6 months

Study Arms (2)

Part A

EXPERIMENTAL

Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine 2 doses of narmafotinib to be explored in Part B.

Drug: narmafotinib ascending doses

Part B

EXPERIMENTAL

Part B will determine the efficacy of 2 doses of narmafotinib selected from Part A

Drug: narmafotinib dose comparison

Interventions

narmafotinib ascending doses DRUG

once daily capsules

Part A

narmafotinib dose comparison DRUG

once daily capsules

Part B

Eligibility Criteria

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

You may qualify if:

• Aged at least 18 years at the time of consent.
• Confirmed diagnosis of metastatic pancreatic adenocarcinoma (PDAC) within the 6 weeks prior to study start and have not received treatment for metastatic PDAC.
• Have measurable disease by RECIST v1.1.
• Eligible for treatment with mFOLFIRINOX as standard of care therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Have a life expectancy of \> 3 months.
• Adequate organ function
• Agree to use effective contraception.

You may not qualify if:

• Pregnant or breast-feeding
• Have received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -7.
• Neuroendocrine or acinar cell pancreas tumors.
• Known brain metastases.
• Conditions that could interfere with the swallowing or absorption of study medication.
• Received previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
• Received cytotoxic doses of any 5-FU based chemotherapy.
• Any chemotherapy related toxicities greater than grade 1 from prior neoadjuvant or adjuvant therapy for PDAC.
• Human immunodeficiency virus (HIV) infection and/or history of Hepatitis B infection or known to have active hepatitis B or C.
• Uncontrolled angina, myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 1-year prior to the first dose of study drug.
• History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis.
• Clinical signs of active infection at the time of Screening or Baseline.
• Clinically significant allergies to narmafotinib, mFOLFIRINOX components (or any of their excipients) that are not likely to be well controlled with pre-medication or other supportive measures.
• Any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the mFOLFIRINOX component package inserts.
• Peripheral neuropathy \> Grade 1.

Sponsors & Collaborators

• Amplia Therapeutics Limited: lead

Study Sites (2)

GenesisCare

St Leonards, New South Wales, 2065, Australia

Location

Epworth Healthcare

Richmond, Victoria, 3121, Australia

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A - dose ascending BOIN design Part B - parallel arm (2 dose levels)

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: June 18, 2025
• Study Start: August 18, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)