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

Amplia Therapeutics

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Pancreatic Cancer Metastatic

Treatments

Drug: narmafotinib dose comparison

Drug: narmafotinib ascending doses

Study type

Interventional

Funder types

Industry

Identifiers

NCT07026279

U1111-1298-5990 (Other Identifier)

AMP945-PC-202

Details and patient eligibility

About

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.

Enrollment

67 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

67 participants in 2 patient groups

Part A

Experimental group

Description:

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.

Treatment:

Drug: narmafotinib ascending doses

Part B

Experimental group

Description:

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

Treatment:

Drug: narmafotinib dose comparison