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

A Phase 1b/2a, Multicenter, Open Label Study of the Safety, Efficacy and Pharmacokinetics of Narmafotinib in Combination With Modified FOLFIRINOX in Pancreatic Cancer Patients

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer Metastatic
• Intervention / Treatment: Drug: narmafotinib ascending doses; Drug: narmafotinib dose comparison

• Study Type: Interventional
• Enrollment (Estimated): 67
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • GenesisCare
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Epworth Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Prior treatment with narmafotinib or other FAK inhibitor within the 2 years prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; 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; once daily capsules
Experimental: Part B; Part B will determine the efficacy of 2 doses of narmafotinib selected from Part A	Drug: narmafotinib dose comparison; once daily capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR based on RECIST defined as the time from the date of the first confirmed response to the date of progression or death	Imaging every 56 days per participant, with an expected average duration of 6 months
Overall survival (OS)	OS of participants, defined as time from first dose until death from any cause	Imaging every 56 days per participant, with an expected average duration of 6 months
Progression free survival (PFS)	PFS of participants, defined as time from first dose to date of first observed progression, based on RECIST, or death from any cause (whichever comes first)	Imaging every 56 days per participant, with an expected average duration of 6 months
narmafotinib levels in plasma	Measurement of maximum concentration (Cmax) of narmafotinib	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	Measurement of time to Cmax (tmax) of narmafotinib	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	Measurement of clearance of narmafotinib	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)	ORR based on RECIST 1.1	Imaging every 56 days per participant, with an expected average duration of 6 months
Clinical benefit rate (CBR)	CBR defined as the proportion of patients with complete response (CR) + partial response (PR) + stable disease (SD) with SD for at least 6 months	Imaging every 56 days per participant, with an expected average duration of 6 months
Disease control rate (DCR)	DCR based on RECIST defined as the proportion of participants who achieve complete response (CR), partial response (PR) or stable disease (SD)	Imaging every 56 days per participant, with an expected average duration of 6 months

Collaborators and Investigators

• Sponsor: Amplia Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: June 10, 2025
• First Posted (Actual): June 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pancreatic cancer; Pancreatic Ductal Adenocarcinoma; PDAC
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: AMP945-PC-202; U1111-1298-5990 (Other Identifier: WHO)

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