MEDI4736 With Selumetinib for KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Study Groups:

If participant is found to be eligible to take part in this study, participant will be
randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no
one knows if one study group is better, the same, or worse than the other group.

- If participant is in Group 1, participant will take selumetinib 2 times each day.

- If participant is in Group 2, participant will take selumetinib 2 times each day on Days
1-7 and 15-22 of each study cycle.

All participants will also receive MEDI4736.

Study Drug Administration:

Each study cycle is 28 days.

Participant should take each dose of selumetinib about 12 hours apart after fasting (having
nothing to eat or drink except water) for 1 hour before and 2 hours after taking selumetinib.
Participant will follow the dosing schedule to which participant has been assigned (as
described above under Study Groups).

Participant should record each selumetinib dose in the dosing diary that will be given to
participant. Participant should bring the diary to participant's study visits at the end of
every cycle.

Both groups will receive MEDI4736 by vein over about 60 minutes on Day 1 of every cycle.

Participant will be given standard drugs to help decrease the risk of side effects.
Participant may ask the study staff for information about how the drugs are given and their
risks.

Length of Study:

Participant may receive the study drugs for as long as the doctor thinks is in participant's
best interest. Participant will no longer be able to take the study drugs if the disease gets
worse, if intolerable side effects occur, or if participant is unable to follow study
directions.

Participation on the study will be over after the Follow-Up Period.

Study Visits:

About 14 days before the first dose of the study drugs:

- Participant will have a physical exam.

- Blood (about 3 teaspoons) and urine will be collected for routine tests.

- If the doctor thinks it is needed, participant will have an EKG.

On Day 1 of every cycle:

- Participant will have a physical exam.

- Blood (about 3 teaspoons) and urine will be collected for routine tests.

- If the doctor thinks it is needed, participant will have an eye exam.

- If participant can become pregnant and the doctor thinks it is needed, blood (about ½
teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycle 1 and at Week 16, participant will have an EKG. Participant will have
triplicate EKGs on Day 1 of Cycle 1.

At Week 8 and about every 8 weeks after that, participant will have a CT scan or MRI to check
the status of the disease.

At Week 12 and about every 12 weeks after that, participant will have an ECHO or multigated
acquisition (MUGA) scan.

End-of-Study Visits:

At about 30 days and 90 days after participant's last dose of the study drugs:

- Participant will have a physical exam.

- Blood (about 3 teaspoons) will be drawn for routine tests.

- Participant will have an EKG.

- If participant can become pregnant and the doctor thinks it is needed, blood (about ½
teaspoon) or urine will be collected for a pregnancy test.

Follow Up Period:

About every 6 months, participant will be called by a member of the study staff to ask how
participant is doing and if participant has started any new treatments outside of the study.
These calls should last about 10 minutes each time.

If the doctor thinks it is needed, participant may return to the clinic for either a CT scan
or MRI to check the status of the disease.

This is an investigational study. MEDI4736 and selumetinib are not FDA approved or
commercially available. They are currently being used for research purposes only. The study
doctor can explain how the study drugs are designed to work.

Up to 76 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Histologically or cytologically confirmed recurrent non-small cell lung cancer not
amendable to curative intent therapy or stage IV NSCLC.

2. Known KRAS mutation status by CLIA certified test. Patients in the safety run-in are
not required to have a tumor with mutant KRAS. In the randomized portion of the trial,
only patients with KRAS mutation are eligible.

3. Documented progression following at least one line of chemotherapy for metastatic or
recurrent disease, or progression within 6 months of receiving adjuvant chemotherapy
or concurrent chemotherapy for early stage or locally advanced disease.

4. Biopsy accessible disease and willingness to undergo tumor biopsy.

5. Measurable disease by RECIST 1.1.

6. Age>/= 18 years.

7. ECOG performance status 0 or 1.

8. Ability to take pills by mouth.

9. Patients must have normal organ and marrow function as defined: leukocytes
>/=3,000/mcL, absolute neutrophil count >/=1,500/mcL, platelets >/=100,000/mcL,
hemoglobin >/9.0g/dL, total bilirubin allowed if in the setting of known Gilbert's disease), AST(SGOT)/ALT(SGPT) institutional upper limit of normal or Alkaline phosphatase metastases are present, creatinine clearance >/=50 mL/min/1.73^2 by Cockcroft-Gault
equation (creatinine clearance= ([140-age]x body mass)/(plasma creatinine x 72) x
gender correction factor) or by 24-hour urine collection.

10. Brain metastases are allowed, as long as they are stable and do not require treatment
with anticonvulsants or escalating doses of steroids.

11. Females of childbearing potential must have a negative serum pregnancy test and must
agree to use adequate contraception for the duration of the study and six months
after. Females 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). Continued in #12

12. Continued from #11: a) Acceptable effective methods of contraception for women include
implants, injectables, combined oral contraceptives, some intrauterine devices/systems
and sterilization including vasectomy of the partner, all being used in combination
with barrier methods of contraception (e.g. condoms). b) True sexual abstinence is
also an acceptable method of contraception. Continued in #13

13. Continued from #12: Women will be considered post-menopausal if they have been
amenorrheic for the past 12 months without an alternative medical cause. The following
age-specific requirements must also apply: i.)Women < 50 years old: they would be
considered post-menopausal if they have been amenorrheic for the past 12 months or
more following cessation of exogenous hormonal treatments. The levels of Luteinizing
Hormone (LH) and Follicle-Stimulating Hormone (FSH) must also be in the
post-menopausal range (as per the institution). ii.)Women >/= 50 years old: they would
be consider post-menopausal if they have been amenorrheic for the past 12 months or
more following cessation of all exogenous hormonal treatments, or have had
radiation-induced oophorectomy with the last menses > 1 year ago, or have had
chemotherapy-induced menopause with >1 year interval since last menses, or have had
surgical sterilisation by either bilateral oophorectomy or hysterectomy.

14. Non-sterilized males who are sexually active with a female partner of childbearing
potential must use adequate contraception for the duration of the study and 90 days
after the last dose of study medication. a) Acceptable methods of contraception for
men include the use of condoms with spermicidal foams/gels or prior vasectomy. b) True
sexual abstinence is also an acceptable method of contraception.

15. Ability to understand and the willingness to sign a written informed consent document.

16. Have adequate renal function, with a GFR of >/= 50ml/min by the Cockcroft-Gault
formula or by 24 hour urine collection.

Exclusion Criteria:

1. Have received or are receiving an investigational medicinal product (IMP) or other
systemic anticancer treatment within 4 weeks prior to the first dose of study
treatment, or within a period during which the IMP or systemic anticancer treatment
has not been cleared from the body (e.g. a period of 5 'half-lives'), whichever is the
most appropriate and as judged by the investigator.

2. Current or prior use of immunosuppressive medication within 14 days of the 1st dose of
durvalumab, with the exception of intranasal and inhaled corticosteroids or oral
corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid.

3. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
treatment.

4. Receipt of radiation therapy within 4 weeks prior to starting study treatment. Limited
field of radiation for palliation at any time prior to the start of study treatment is
acceptable if: i.) The lung is not in the radiation field ii.) The irradiated lesions
are not used as target lesions.

5. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab.

6. Prior treatment with a MEK, Ras, or Raf inhibitor, or CTLA4 inhibitor.

7. Patients who are receiving any other investigational agents.

8. Have any unresolved chronic toxicity with CTCAE grade >/= 2, from previous anticancer
therapy, except for alopecia.

9. Known hypersensitivity to selumetinib or durvalumab or any excipient or history of
allergic reactions attributed to compounds of similar chemical or biologic composition
to selumetinib or durvalumab.

10. Active or prior documented autoimmune disease within the past 3 years. Patients with a
history of vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
(within the past 2 years) are not excluded.

11. Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,
ulcerative colitis).

12. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, has been treated with surgery and / or radiation, and
has been stable without requiring corticosteroids nor anti-convulsant medications for
at least 4 weeks prior to the first dose of study medication.

13. Known history of previous clinical diagnosis of tuberculosis.

14. History of primary immunodeficiency.

15. History of organ transplant requiring therapeutic immunosuppression.

16. Cardiac conditions as follows: i.) Mean QT interval corrected for heart rate (QTc)
>/=450 ms calculated from 3 ECGs using Fredericia's formula [QTcF] or other factors
that increase the risk of QT prolongation. ii.) Uncontrolled hypertension (BP >/=
150/95 despite optimal medical therapy). iii.) Acute coronary syndrome within 6 months
prior to starting treatment. iv.) Uncontrolled Angina - Canadian Cardiovascular
Society grade II-IV despite medical therapy. v.) Symptomatic heart failure NYHA Class
II-IV, prior or current cardiomyopathy, or severe valvular heart disease. - Criteria
continued in #17

17. Continued from #16: vi.) Prior or current cardiomyopathy including but not limited to
the following: a) known hypertrophic cardiomyopathy b) known arrhythmogenic right
ventricular cardiomyopathy c) previous moderate or severe impairment of left
ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA)
even if full recovery has occurred. vii.) Baseline Left ventricular ejection fraction
(LVEF) below the LLN or <55% measured by echocardiography or institution's LLN for
MUGA. viii.) Severe valvular heart disease. ix.) Atrial fibrillation with a
ventricular rate > 100 bpm on ECG at rest.

18. Ophthalmologic conditions as follows: i.) Current or past history of retinal pigment
epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein
occlusion. ii.) Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
(irrespective of IOP).

19. Any gastrointestinal disorder expected to limit absorption of selumetinib

20. History of another primary malignancy within 5 years prior to starting study
treatment, except for adequately treated basal or squamous cell carcinoma of the skin
or cancer of the cervix in situ

21. Recent major surgery within 4 weeks prior to starting study treatment, with the
exception of surgical placement for vascular access.

22. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
B, hepatitis C, HIV, and active clinical tuberculosis), active bleeding diatheses or
renal transplant; ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or
gastritis, or psychiatric illness/social situations that would limit compliance with
study requirements.

23. Pregnant or breastfeeding women.

24. Receiving or have received systemic anti-cancer therapy within 4 weeks prior to
starting study treatment (6 weeks for nitrosoureas, mitomycin, and suramin), or any
anticancer therapy which has not been cleared from the body by the time of starting
study treatment.

25. Have evidence of any other significant clinical disorder or laboratory finding that,
as judged by the investigator, makes it undesirable for the patient to participate in
the study.

26. Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g.,
inflammatory bowel disease), or significant bowel resection that would adversely
affect the absorption / bioavailability of the orally administered study medication.

27. Are male or female patients of reproductive potential and, as judged by the
investigator, are not employing an effective method of birth control.

28. Patient weight less than 30 kg.