To Assess the Safety of Continuous IV Administration of Plerixafor and Assess Impact on the Immune Microenvironment in Patients With Pancreatic, Ovarian and Colorectal Adenocarcinomas

This is a prospective, non-randomised, open label, Phase I, dose escalation trial of
plerixafor in patients with histological documentation of advanced pancreatic, high grade
serous ovarian or colorectal adenocarcinoma. We will investigate the feasibility of
administering plerixafor in terms of safety, and will try to identify the proof of mechanism
in patients. This trial will follow the standard 3+3, Phase I trial design, leading to a
treatment expansion phase to confirm the RP2D.

Inclusion Criteria:

- Aged 16 years or over (In the US, aged 18 years or over only).

- Dose escalation phase only: Patients with inoperable, histologically proven locally
advanced or metastatic pancreatic, high grade serous ovarian or colorectal
adenocarcinoma, refractory to conventional chemotherapy or a patient who has declined
conventional chemotherapy OR;

- Treatment expansion phase only: Patients with inoperable, histologically proven
locally advanced or metastatic pancreatic, refractory to conventional chemotherapy or
a patient who has declined conventional chemotherapy.

- Tumour lesions considered to be accessible for core biopsy and immunostaining
assessment.

- ECOG performance status 0-1.

- Life expectancy of at least 12 weeks.

- All women of child-bearing potential and all sexually active male patients must agree
to use effective contraception methods throughout the trial and for 3 months after the
final dose of trial drug.

Exclusion Criteria:

- Inadequate haematological function defined by:

- Absolute neutrophil count (ANC) <1.5 x 109/L

- Absolute lymphocyte count <1.0 x 109/L (counts shall be rounded to the nearest
tenth. (e.g. 0.96 will be rounded to 1.0 x 109/L))

- Haemoglobin <9.0 g/dL (90 g/L) (may be increased to this level with transfusion
as long as there is no evidence of active bleeding)

- Platelets <100 x 109/L

- Clotting; INR >1.3

- Inadequate renal function defined by calculated creatinine clearance by
Cockcroft-Gault of <50 ml/min.

- Inadequate hepatic function defined by:

- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x
upper limit of normal (ULN) or >5 x in the presence of liver metastases

- Total bilirubin >1.5 x ULN

- Current treatment (within 28 days of entry) with chemotherapy, steroids or other
immunosuppressive drugs.

- Significant acute or chronic medical or psychiatric condition, disease or laboratory
abnormality which in the judgment of the Investigator would place the patient at undue
risk or interfere with the trial.

- Cardiac co-morbidity:

- Past history of significant rhythm disturbance (e.g. SVT, AF or ventricular
irregularities)

- Requirement for pacemaker

- Myocardial infarction in the previous 6 months

- Known medical history of proven postural hypotension.

- Active infection.

- Patients with known allergy to plerixafor or its excipients.

- Patients known to have hepatitis B, hepatitis C or HIV infection.

- Participation in any other interventional clinical trial

- Women, who are pregnant, plan to become pregnant or are lactating (during the trial or
for up to 3 months after the last dose)