AZD9150 With MEDI4736 in Patients With Advanced Pancreatic, Non-Small Lung and Colorectal Cancer

Study Drug Administration:

Every study cycle will be 28 days.

If you are found to be eligible to take part in this study, you will begin study treatment
within 28 days after the screening tests are performed. You will receive AZD9150 by vein over
1 hour 3 times before the first dose of MEDI4736 (7, 5, and 3 days beforehand), and then on
Days 1, 8, 15, and 22 of every cycle.

You will receive MEDI4736 by vein over about 1 hour on Day 1 of every cycle, about 30 minutes
after the AZD9150 infusion.

Length of Treatment:

You may continue receiving the study drugs for as long as the doctor thinks is in your best
interest. You will no longer be able to receive the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Study Visits:

On Day 1 of Cycle 1 and beyond:

- You will have a physical exam.

- Blood (about 4 teaspoons) and urine will be collected for routine tests.

- Blood (about 2 teaspoons) will be drawn to check your thyroid function.

- If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a
pregnancy test.

On Days 8 and 22 of Cycles 1 and beyond:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests (Cycle 1 only).

On Day 15 of Cycles 1 and beyond:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests.

- Urine will be collected for routine tests (Cycle 1 only).

On Day 22 of Cycles 1 and beyond:

- Blood (about 2½ tablespoons) will be drawn for biomarker testing.

- You will have a core tumor biopsy for biomarker testing.

Every 2 months, you will have a PET/CT scan or MRI to check the status of the disease.

End-of-Treatment Visit:

About 30 days after your last dose of the study drugs:

- You will have a physical exam.

- Blood (about 4 tablespoons) and urine will be collected for routine tests.

- Blood (about 2 teaspoons) will be drawn to check your thyroid function.

- Blood (about 2½ tablespoons) will be drawn for biomarker testing.

- You will have a PET/CT scan or MRI to check the status of the disease.

- If you can become pregnant, urine will be collected for a pregnancy test.

Follow-Up:

About 1-3 months after your last dose of the study drugs, you will have a PET/CT scan or MRI
to check the status of the disease.

If you cannot come to MD Anderson for your follow-up visits, you may be called every 12 weeks
and asked about how you are doing. These calls will last about 10 minutes each.

Your participation on the study will be over at the end of the follow-up period.

Treatment Beyond Progression:

If the disease appears to be getting worse or the tumors appear to be getting larger, you may
still be able to receive the study drugs if you and your doctor decide it is in your best
interest. The study doctor will discuss this option with you. If you choose to receive the
study drugs after the disease gets worse, you will sign an additional informed consent form.

Inclusion Criteria:

1. The patient/legal representative must be able to read and understand the informed
consent form (ICF) and must have been willing to give written informed consent and any
locally required authorisation (eg, Health Insurance Portability and Accountability
Act in the USA; European Union Data Privacy Directive in the EU) before any
study-specific procedures, including screening evaluations, sampling, and analyses.

2. Has a histological confirmation of pancreatic cancer, mismatch deficient colorectal
cancer, or NSCLC that is refractory to standard therapy or for which no standard of
care regimen currently exists.

3. Male and female patients must be at least 18 years of age.

4. Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.

5. Has measurable disease, defined as at least 1 lesion that can be accurately measured
in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm
by computerised tomography (CT) scan, except lymph nodes which must have minimum short
axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases).
Indicator lesions must not have been previously treated with surgery, radiation
therapy, or radiofrequency ablation unless there is documented progression after
therapy.

6. Has adequate organ and marrow function as defined below. Transfusions intended to
elevate any parameters below solely for the intent of meeting study eligibility are
not permitted. Leukocytes >/=3000 mcL, Absolute neutrophil count >/=1500 mcL,
Platelets >/=100 000 mcL, Hemoglobin >/=9 g/dL, Total bilirubin bilirubin hyperbilirubinaemia) or in the presence of liver metastases, ALT and AST no demonstrable liver metastases or Creatinine within normal limits OR, for patients with levels above institutional
normal: Creatinine clearance measured by 24-hour urine collection >/=60 mL/min, OR
Calculated corrected creatinine clearance >/=60 mL/min/1.73 m^2 using the
Cockcroft-Gault formula (Cockcroft and Gault 1976) corrected for the body surface
area.

7. Women of childbearing potential and men who are sexually active with a female partner
of childbearing potential must be surgically sterilised, practicing abstinence, or
agree to use 2 birth control methods before study entry, for the duration of study
participation, and for 20 weeks after the final dose of study drug; cessation of birth
control after this point should be discussed with a responsible physician. Women of
childbearing potential are defined as those who are not surgically sterile (ie,
bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or
postmenopausal (defined as 12 months with no menses without an alternative medical
cause). Two methods of contraception which are considered accurate per protocol must
be combined. Periodic abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of birth control.

8. Women of childbearing potential also may not be breast feeding and must have a
negative serum or urine pregnancy test within 72 hours before the start of study
treatment.

9. The patient/legal representative must be willing to provide written consent for
collection of formalin fixed paraffin-embedded blocks or slides from archival
diagnostic histology samples, where available.

Exclusion Criteria:

1. Has a spinal cord compression unless asymptomatic, radiographically stable over the
last 4 weeks, and not requiring steroids for at least 4 weeks before the start of
study treatment.

2. Presently has a second malignancy other than SCCHN, or history of treatment for
invasive cancer other than SCCHN in the past 3 years. Exceptions are: Previously
treated in-situ carcinoma (ie, noninvasive), Cervical carcinoma stage 1B or less,
Noninvasive basal cell and squamous cell skin carcinoma, Radically treated prostate
cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not
requiring ongoing antiandrogen hormonal therapy

3. Patients must have completed previous cancer-related treatments before enrollment. Any
concurrent chemotherapy, radiotherapy, immunotherapy, or biologic, or hormonal therapy
for cancer excludes the patient (concurrent use of hormones for noncancer-related
conditions [eg, insulin for diabetes or hormone replacement therapy] is acceptable).
The following intervals between end of the prior treatment and first dose of study
drug must be observed: Port-a-cath placement: no waiting required. Minor surgical
procedures: >/=7 postoperative days. Major surgery: >/=4 weeks. Radiotherapy: >/=4
weeks. Chemotherapy: >/=4 weeks. Immunotherapy or investigational anticancer therapy
with agents other than mAbs: >/=4 weeks. Immunotherapy or investigational anticancer
therapy with mAbs: >/=6 weeks. Immunosuppressive medication: >/=4 weeks with the
exceptions of intranasal or inhaled corticosteroids or systemic corticosteroids at
physiologic doses not to exceed 10mg/day of prednisone or equivalent.

4. Is still experiencing toxicity related to prior treatment and assessed as CTCAE grade
>1. Exceptions are alopecia and/or anorexia. The eligibility of patients who are still
experiencing irreversible toxicity that is not reasonably expected to be exacerbated
by the study drugs in this study (eg, hearing loss) must be reviewed and approved by
both the Principal Investigator and Medical Monitor.

5. Has experienced immune-related AEs (irAEs) while receiving prior immunotherapy
(including anti-CTLA4 treatment) and assessed as CTCAE grade >/= 3

6. Has active or prior documented autoimmune disease within the past 2 years with the
exceptions of vitiligo, Grave's disease, and/or psoriasis not requiring systemic
treatment

7. Has active or prior documented inflammatory bowel disease (eg, Crohn's disease,
ulcerative colitis)

8. Has a history of primary immunodeficiency

9. Has undergone an organ transplant that requires use of immunosuppressive treatment

10. Has a history of interstitial lung disease or pneumonitis from any cause

11. Has a history of allergic reactions attributed to the study treatments (AZD9150 or
MEDI4736), their compounds, or agents of similar chemical or biologic composition (eg,
antibody therapeutics)

12. Suffers from a comorbidity that in the opinion of the Investigator renders the patient
unsuitable for participation in the study. Such comorbidity may include, but is not
limited to, uncontrolled intercurrent illness such as active infection, severe active
peptic ulcer disease or gastritis, myocardial infarction within 6 months before entry,
congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy,
unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or
psychiatric illness/social situations that would limit compliance with study
requirements.

13. As judged by the Investigator, has any evidence of severe or uncontrolled systemic
diseases such as active bleeding diatheses, is positive for human immunodeficiency
virus (HIV), or has active hepatitis B virus (HBV) and/or hepatitis C virus (HCV)

14. Has a known history of tuberculosis

15. Has a condition that, in the opinion of the Investigator, would interfere with the
evaluation of the study drugs or the interpretation of patient safety or study results

16. Has received a live attenuated vaccine within 28 days before the first dose of study
drug

17. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements

18. Patients with clinically active brain metastases (known or suspected) are excluded
unless the brain metastases have been previously treated and are considered stable.
Stable brain metastases are defined as no change on CT scan or magnetic resonance
imaging (MRI) scan for a minimum of 2 months AND no change in steroid dose for a
minimum of 4 weeks, unless change due to intercurrent infection or other acute event.

19. Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control