Overview

AMP946 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer

Status:
Not yet recruiting
Trial end date:
2025-05-01
Target enrollment:
0
Participant gender:
All
Summary
This is a multicentre, open label, two-part study to determine whether 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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Amplia Therapeutics Limited
Criteria
Inclusion Criteria:

1. Provide written informed consent prior to any study procedures and agree to adhere to
all protocol requirements.

2. Aged at least 18 years at the time of consent.

3. 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.

4. 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.

5. Eligible for treatment with nab-paclitaxel and gemcitabine as standard of care
therapy.

6. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1, sustained on two
separate assessments: the first at least 2 weeks prior to the 1st dose 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.

7. Has a life expectancy of >3 months.

8. Adequate organ function, as defined by the laboratory results below (samples must be
obtained ≤14 days prior to study drug administration):

a) Haematology:

(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.

9. Agree to use contraception according to protocol

Exclusion Criteria:

1. Pregnant or breast-feeding, or plans to become pregnant during the study.

2. Has received any investigational medicinal product (IMP) within 30 days or 5
half-lives (whichever is longer) prior to Day -8.

3. 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).

4. Gastrointestinal condition that could interfere with the swallowing or absorption of
study medication.

5. 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.

6. 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.

7. History of malignancy other than in situ cancer or basal or squamous cell skin cancer
in the last 5 years.

8. Major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy
for diagnosis without removal of an organ), within 4 weeks prior to Day -8.

9. Known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections
or known to be positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C
Antibody.

10. Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular
accident within 6 months prior to the first dose of study drug.

11. Focal palliative radiotherapy (e.g., to a bony metastasis) within the 14 days prior to
Run-in, or more extensive radiotherapy within 28 days prior to Run-in.

12. History of chronic leukemias (e.g., chronic lymphocytic leukemia).

13. History of interstitial lung disease, history of slowly progressive dyspnoea and
unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
hypersensitivity pneumonitis or multiple allergies.

14. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).

15. Clinical signs of active infection and/or a temperature of > 38.0°C at the time of
Screening or Baseline. Study entry may be deferred at the discretion of the Principal
Investigator (PI).

16. Currently using warfarin.

17. Administration of a live virus vaccine in the 4 weeks prior to Day -8 or plans to
receive a live virus vaccine during the study.

18. Clinically significant allergies to AMP945, nab-paclitaxel or gemcitabine (or any of
their excipients), including hypersensitivity reactions to human albumin, that are not
likely to be well controlled with premedication or other supportive measures.

19. Exhibiting any of the conditions or events outlined in the Contraindications or
Special Warnings and Precautions sections of the nab-paclitaxel and/or gemcitabine
package inserts.

20. Peripheral neuropathy > Grade 1.

21. Corrected QT interval using Fridericia's correction (QTcF) > 460 ms for males and >480
ms for females.

22. Any clinically relevant medical, social, or psychiatric conditions, or any finding
during Screening, which in the Investigator's opinion may put the participant at
unacceptable risk or interfere with the study objectives.

23. Prior treatment with AMP945.