A Study to Investigate Biomarker Effects of Pre-Surgical Treatment With DNA Damage Repair (DDR) Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

Patients are dosed for a minimum of nine days with drug. Surgery or biopsy can then take
place at any time between Day 10 and Day 21 (depending on when it can be scheduled), but must
occur with 24 hrs following three consecutive treatment days. During the treatment period,
safety assessments must be completed at least weekly.

Follow-up will be completed after surgical resection or biopsy has been completed and can be
part of standard post-surgery follow-up. If this follow-up visit occurs prior to 30 days
after the final dose, a further visit or telephone call must be conducted to assess that any
toxicity has resolved and to check for late toxicity.

Pertinent Inclusion Criteria:

- Provision of informed consent

- Aged at least 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no
deterioration over the previous 2 weeks and an estimated life expectancy of greater
than 12 weeks

- Newly diagnosed, treatment naive, HNSCC suitable for surgical resection or biopsy with
planned radical radiotherapy and/or chemotherapy after surgery or biopsy. Patients who
are suitable for radical chemoradiation without surgery are eligible if they are
willing to undergo an on-treatment (core or surgical) biopsy

- Females must be using adequate contraceptive measures, must not be breast feeding and
must have a negative pregnancy test prior to start of dosing if of child-bearing
potential or must have evidence of non-child-bearing potential

- For the duration of the study and for 6 months after the last study drug
administration, sexually active male patients must be willing to use barrier
contraception i.e., condoms with all sexual partners

- No previous cancer treatment with any cytotoxic agent for this malignancy

- Provision of genetics research informed consent

Pertinent Exclusion Criteria:

- Involvement in the planning and/or conduct of the study

- Previous treatment with a DDR agent

- Participation in another clinical study with an investigational product during the
last 21 days or 5 half-lives of the investigational product, whichever is longer

- Receiving, or having received during the week prior to first dose, corticosteroids at
a dose > 10 mg prednisone/day or equivalent for any reason

- Known hypersensitivity or contraindication to any of the investigational agents or
their excipients

- Small molecule investigational medicinal products (IMPs) within 28 days prior to first
dose; biological IMP within 42 days prior to first dose

- Receiving, or received, concomitant medications, herbal supplements and/or foods that
significantly modulate Cytochrome P450 3A4 (CYP3A4) inhibitors or moderate Cytochrome
P450, family 3, subfamily A (CYP3A) inhibitors, strong CYP3A inducers or moderate
CYP3A inducers

- Impaired hepatic or renal function,inadequate bone marrow reserve or organ function

- Cardiac dysfunction defined as: Myocardial infarction within six months of study
entry, New York Heart Association (NYHA) Class II/III/IV heart failure, unstable
angina, unstable cardiac arrhythmias or reduced LVEF < 55%

- Any of the following cardiac criteria: Mean resting corrected QTc interval using the
Fridericia formula (QTcF) greater than 450 msec/male and greater than 470 msec/female
or congenital long QT syndrome, clinically important abnormalities in rhythm,
conduction or morphology of resting electrocardiography (ECG), factors that increase
the risk of QTc prolongation or risk of arrhythmic events, patients at risk of brain
perfusion problems, relative hypotension (<100/60 mm Hg) or clinically relevant
orthostatic hypotension (>20 mm Hg), uncontrolled hypertension

- Any other malignancy which has been active or treated within the past three years
(except cervical intra-epithelial neoplasia and non-melanoma skin cancer)

- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication

- Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection

- Judgement by the Investigator that the patient should not participate in the study

- Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with
features suggestive of MDS/AML

- Previous allogenic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT)

- Non-leukocyte depleted whole blood transfusion within 120 days of the date of
patient's start on the study