Inclusion Criteria:

          1. Part A (dose escalation):

             Patients with histologically or cytologically confirmed malignant advanced solid
             tumours refractory to standard therapy or for which no suitable effective standard
             therapy exists, including, but not limited to patients with PIK3CA mutant cancers, or
             those with somatic mutations or other aberrations known to result in a hyperactivated
             PI3K-AKT pathway.

             Advanced breast cancer with the following features:

               -  ER+ve breast cancer that has progressed on at least one line of prior endocrine
                  therapy, or

               -  PIK3CA mutant breast cancer progressed on at least one line of prior endocrine
                  therapy or chemotherapy

               -  breast cancer refractory to standard treatment

             Part B (dose expansion):

             Patients with histologically or cytologically advanced solid tumours who have
             progressed on at least one prior chemotherapy regimen for advanced cancer with a
             PIK3CA mutation detected from tumour and/or circulating tumour DNA. Patients with HER2
             positive breast cancer should have progressed on at least two prior HER2 directed
             therapies for advanced breast cancer.

             Cohort B1: ER+ve and HER2-ve post-menopausal breast cancer that has progressed on at
             least one prior hormone therapy for advanced breast cancer.

             Cohort B2: Advanced PIK3CA mutant solid tumours, including but not limiting to triple
             negative and/or HER2 positive breast cancers and lung, head and neck cancers.

             NB. PIK3CA mutation may be assessed in archival tumour samples, fresh tumour samples,
             or in circulating free DNA extracted from plasma or serum. A mutation will be
             considered pathogenic if described to be recurrent somatic mutation in COSMIC
             (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/). Other cancers with
             relevant genetic aberrations (e.g. KRAS mutations) may be considered, depending on
             emerging preclinical and clinical data on these novel antitumour agents

          2. Part A: Measurable disease as assessed by RECIST 1.1 OR evaluable disease. Part B1:
             Measurable disease as assessed by RECIST 1.1 Part B2: Measurable disease as assessed
             by RECIST 1.1 OR evaluable disease

          3. Life expectancy of at least 12 weeks

          4. World Health Organisation (WHO) performance status of 0-1 with no significant
             deterioration over the previous 2 weeks

          5. Haematological and biochemical indices within the ranges shown below. These
             measurements must be performed within one week (Day -7 to Day 1) before the patient
             goes in the trial.

             Haemoglobin (Hb) ≥ 10.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥
             100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients
             with documented Gilberts' disease Alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5
             x ULN is permissible

             Creatinine:

             If creatinine > 1.5 times ULN then:

             Either:

             Calculated creatinine clearance ≥ 50 mL/min (uncorrected value)

             Or:

             Isotope clearance measurement ≥ 50mL/min (corrected)

             Coagulation:

             INR <1.5 APTT <1.5x ULN

          6. Female patients with reproductive potential must have a negative urine or serum
             pregnancy test within 7 days prior to start of trial. Both women and men must agree to
             use a medically acceptable method of contraception throughout the treatment period and
             for 3 months after discontinuation of treatment.

          7. 18 years of age or over with written (signed and dated) informed consent and be
             capable of co-operating with treatment and follow-up.

        Exclusion Criteria:

          1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or
             chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C)
             and 4 weeks for investigational medicinal products before treatment, except for
             hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for
             medical castration in patients with castrate resistant prostate cancer, which are
             permitted, and bisphosphonates or RANK ligand antagonists that are permitted for the
             management of bone metastases. Palliative radiotherapy is acceptable if given for bony
             metastases as long as these are not indicative of disease progression. Study drug must
             be stopped 3 days before radiotherapy and restarted within 28 days, as long as bone
             marrow function has returned to normal.

          2. Patients with prior exposure to both a CDK4/6 inhibitor and a PI3K/ATK/mTOR inhibitor
             are excluded from the study. Patients with prior exposure to either a PI3K/AKT/mTOR
             pathway inhibitor OR a CDK4/6 inhibitor (but not both) are allowed entry into the
             trial provided that adverse effects have recovered to grade 1 or less. Prior exposure
             to fulvestrant is permitted.

          3. Clinically significant abnormalities of glucose metabolism as defined by any of the
             following:

               -  Diagnosis of diabetes mellitus types I or II (irrespective of management).

               -  Glycosylated haemoglobin (HbA1C) ≥7.0% at screening

               -  Fasting Plasma Glucose ≥ 8.3mmol/L at screening. Fasting is defined as no caloric
                  intake for at least 8 hours.

          4. DLCO ≤ 50% of predicted value corrected for hematocrit prior to initiation of study
             treatment.

          5. On-going toxic manifestations of previous treatments ≥ grade 1. Exceptions to this are
             alopecia or certain other toxicities, which in the opinion of the Investigator should
             not exclude the patient.

          6. History of malabsorption syndrome or other condition that would interfere with enteral
             absorption. For example active intestine inflammation (e.g., Crohn's disease or
             ulcerative colitis) requiring immunosuppressive therapy.

          7. History of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis)

          8. Inability or unwillingness to swallow pills, or (for patients receiving fulvestrant)
             receive IM injections.

          9. Known untreated or active central nervous system (CNS) metastases (progressing or
             requiring corticosteroids for symptomatic control). Patients with a history of treated
             CNS metastases are eligible, provided they meet all of the following criteria:

               -  Evaluable or measurable disease outside the CNS is present.

               -  Radiographic demonstration of improvement upon the completion of CNS-directed
                  therapy and no evidence of interim progression between the completion of
                  CNS-directed therapy and the baseline disease assessment for at least 28 days.

               -  Not requiring dexamethasone treatment

         10. Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4
             weeks of the first dose of study treatment

         11. Ability to become pregnant (or already pregnant or lactating). However, those female
             patients who have a negative serum or urine pregnancy test before enrolment and agree
             to use two highly effective forms of contraception (oral, injected or implanted
             hormonal contraception and condom, have a intra-uterine device and condom, diaphragm
             with spermicidal gel and condom) for four weeks before entering the trial, during the
             trial and for six months afterwards are considered eligible.

         12. Male patients with partners of childbearing potential (unless they agree to take
             measures not to father children by using one form of highly effective contraception
             [condom plus spermicide] during the trial and for six months afterwards). Men with
             pregnant or lactating partners should be advised to use barrier method contraception
             (for example, condom plus spermicidal gel) to prevent exposure to the foetus or
             neonate.

         13. At high medical risk because of severe or uncontrolled systemic disease, such as:

             uncontrolled hypertension, symptomatic congestive heart failure ≥ class 2 (refer to
             appendix 4 for grading), unstable angina pectoris, stroke or myocardial infarction
             within 6 months, serious cardiac arrhythmia requiring treatment, with the exceptions
             of atrial fibrillation and paroxysmal supraventricular tachycardia or conduction
             abnormality that has been treated and for which the patient is no longer at risk for
             serious arrhythmia (e.g., Wolff-Parkinson-White syndrome treated with surgical
             ablation)

         14. Clinically significant history of liver disease, including cirrhosis, current alcohol
             abuse, or current known active infection with hepatitis B virus, or hepatitis C virus.

             Active infection is defined as requiring treatment with antiviral therapy or presence
             of positive test results for Hepatitis B (Hepatitis B surface antigen [HBsAg] and/or
             total Hb core antibody [anti-HBc]) or Hepatitis C (Hepatitis C virus [HCV] antibody).
             Unless required by local regulations, patients are not required to have HIV, HCB, or
             HCV assessments at screening if these assessments have not been previously performed.

             Patients who are positive for anti-HBc are eligible only if testing is also positive
             for Hepatitis B surface antibody [HbsAb] and polymerase chain reaction (PCR) is
             negative for HBV DNA.

             Patients who are positive for HCV serology are eligible only if testing for HCV RNA is
             negative.

         15. Immunocompromised status due to current known active infection with HIV or due to the
             use of immunosuppressive therapies for other conditions

         16. Need for current chronic corticosteroid therapy, specifically dexamethasone or ≥ 10 mg
             of prednisone per day or an equivalent dose of other anti inflammatory
             corticosteroids. Stable use (i.e., no change in dose within 1 month prior to Day 1 of
             Cycle 1) of inhaled corticosteroids is allowed.

         17. Prior bone marrow transplant or extensive radiotherapy to greater than 25% of bone
             marrow within eight weeks.

         18. Is a participant or plans to participate in another interventional clinical trial,
             whilst taking part in this Phase I study. Participation in an observational trial
             would be acceptable.

         19. Current malignancies of other types, with the exception of adequately treated
             cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell
             carcinoma of the skin. Cancer survivors, who have undergone potentially curative
             therapy for a prior malignancy, have no evidence of that disease for 3 years or more
             and are deemed at negligible risk for recurrence, are eligible for the trial.

         20. Any other condition which in the Investigator's opinion would not make the patient a
             good candidate for the clinical trial.