Brief Summary
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 cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
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.
Intervention / Treatment
- Drug: AMP945 ascending doses
- Drug: AMP945 RP2D
Inclusion Criteria
- Provide written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. prior to any study procedures and agree to adhere to all protocol requirements.
- Aged at least 18 years at the time of consent.
- Confirmed histological or cytological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of advancedat a late stage, far along pancreatic adenocarcinomacancer arising from mucus-producing glands in organs 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 Oncologythe study, diagnosis and treatment of cancer Group (ECOG) Performance Score of 0-1, sustained on two separate assessments: the first at least 2 weeks prior to the 1st dosethe amount of medication taken of AMP945 and the 2nd within 72 hours prior to the 1st dose of AMP945. Participants not maintaining an ECOG Performance Score of 0-1 at the second assessment will be excluded from participation.
- Has a life expectancy of >3 months.
- Adequate organ function, as defined by the laboratory results below (samples must be obtained ≤14 days prior to study drug administration):
a) Haematologythe study of blood and related diseases:
(i) Absolute neutrophil count (ANC) ≥1.5 × 109/L;
(ii) Platelet count ≥100,000/mm3 (100 × 109/L);
(iii) Haemoglobin (Hgb) ≥9 g/dL.
b) Serum chemistry:
(i) Aspartate transaminase (AST) (SGOT), ALT (SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤5 × ULN is allowed;
(ii) Total bilirubin ≤ULN;
(iii) Creatinine <1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 (calculated using the Cockcroft-Gault equation).
c) No clinically significant abnormalities in coagulation results.
d) No clinically significant abnormalities in urinalysis results.
- Agree to use contraception according to protocol