A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients (AMP945-PC-201)
- Aged at least 18 years at the time of consent.
- Confirmed histological or cytological diagnosis of advanced pancreatic adenocarcinoma that is:
- Part A: metastatic or not surgically resectable.
- Part B: metastatic, with initial diagnosis of metastatic disease ≤6 weeks prior to Baseline.
- Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Eligible for treatment with nab-paclitaxel and gemcitabine as standard of care therapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
- Has a life expectancy of >3 months.
- Adequate organ function, as defined in the protocol
Key Exclusion Criteria:
- Pregnant or breast-feeding, or plans to become pregnant during the study.
- Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -8.
- Known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no oedema, no steroids and stable in 2 scans at least 4 weeks apart).
- Gastrointestinal condition that could interfere with the swallowing or absorption of study medication.
- Part A: Has received prior systemic treatments for pancreatic cancer, except those given in the adjuvant setting, and with recurrence more than 6 months after completion of curative/adjuvant treatment.
- Part B: Has received no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
- History of malignancy other than in situ cancer or basal or squamous cell skin cancer in the last 5 years.
- Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 6 months prior to the first dose of study drug.
- History of chronic leukemias (e.g., chronic lymphocytic leukemia), interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies, connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
- Currently using warfarin.
- Peripheral neuropathy > Grade 1.
This is a multicentre, open label, two-part study to determine whether the focal adhesion kinase (FAK) inhibitor AMP945, when given prior to dosing with gemcitabine and nab-paclitaxel, improves response to therapy in first-line patients with unresectable or metastatic pancreatic cancer.
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 the RP2D of AMP945 to be explored in Part B.
Part B will determine the efficacy of the AMP945 regimen at the RP2D, and will be run as a Simon Two-stage design; Stage 1 will enrol 26 participants. If ≤5 of the 26 participants show an objective response, then recruitment will be paused and a detailed analysis of futility will be performed. If the study is deemed futile, recruitment will cease. If the study is determined to be not futile or >5 of the 26 participants show an objective response, recruitment will continue, and an additional 24 participants will be enrolled in Stage 2.