Lung-MAP: Durvalumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers

CO-PRIMARY OBJECTIVES:

I. To assess the response rate (confirmed and unconfirmed, complete and partial) among
patients treated with durvalumab (MEDI4736).

II. To assess the response rate (confirmed and unconfirmed, complete and partial) among
programmed death ligand 1 (PD-L1) positive patients treated with MEDI4736.

SECONDARY AND EXPLORATORY OBJECTIVES:

I. To assess investigator-assessed progression-free survival (IA-PFS) among patients treated
with MEDI4736.

II. To assess IA-PFS among PD-L1 positive patients treated with MEDI4736. III. To assess
overall survival (OS) in patients treated with MEDI4736. IV. To assess overall survival (OS)
in PD-L1 positive patients treated with MEDI4736.

V. To evaluate the frequency and severity of toxicities associated with MEDI4736.

VI. To assess immune-related IA-PFS using a modified response criteria adapted for
immunotherapy (immune-related response criteria [irRC]-IA-PFS) in all patients and in the
subset of patients determined to be PD-L1 positive treated with MEDI4736.

VII. To compare IA-PFS, irRC-IA-PFS, OS, toxicity and response rates between patients
randomized to MEDI4736 versus docetaxel.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive or prognostic tumor/blood biomarkers beyond the chosen
biomarker.

II. To identify potential resistance biomarkers at disease progression. III. To establish a
tissue/blood repository from patients with refractory squamous cell cancer.

MEDI4736 RE-TREATMENT OBJECTIVES:

I. To evaluate response rates (confirmed and unconfirmed, complete and partial responses)
among patients re-treated with MEDI4736.

II. To estimate median PFS from the date of re-treatment.

OUTLINE (CLOSED TO ACCRUAL 12/18/2015):

Patients with tumors that do not match one of the currently active drug-biomarker
combinations receive durvalumab intravenously (IV) over 60 minutes on day 1. Courses repeat
every 2 weeks for 12 months in the absence of disease progression or unacceptable toxicity.
Upon evidence of progression following discontinuation of 12 months of treatment, patients
may restart treatment and continue for up to 12 additional months (Arm III).

ARM I: (Closed to accrual 12/2015) Patients receive durvalumab intravenously (IV) over 60
minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease
progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 4/2015): Patients receive docetaxel IV on day 1. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity. (closed to
accrual with Revision #2 4/22/15)

ARM III: For patients assigned to Arm 1, MEDI4736: Upon evidence of progression following
discontinuation of 12 months of treatment, patients may restart treatment with Arm 3,
MEDI4736 for up to 12 months with the same treatment guidelines followed during the initial
12-month treatment period. Patients will only be able to restart treatment once; thus a
maximum of two 12-month periods will be allowed. Patients receive durvalumab IV over 60
minutes on day 1. Treatment repeats every 14 days for 12 months in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the
first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Inclusion Criteria:

- Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON
ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master
Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)

- Patients must have been assigned to S1400A

- Patients must not have any prior exposure to immunotherapy such as, but not limited to
anti-programmed death 1 (PD-1) or anti-PD-L1 antibodies; prior exposure to the
following is allowed: anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, live
attenuated vaccines, anti-EGFR agents and sargramostim (GM-GSF)

- Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to
sub-study registration

- Patients must not have any active or prior documented autoimmune or inflammatory
disease (including inflammatory bowel disease, diverticulitis with the exception of
diverticulosis, celiac disease, irritable bowel disease; Wegener syndrome; Hashimoto
syndrome) within 3 years prior to sub-study registration; patients with vitiligo,
alopecia, Grave's disease, or psoriasis requiring systemic treatment within the past 3
years are not eligible

- Patients must not have any history of primary immunodeficiency

- Patients must not have received any immunosuppressive medication within 28 days prior
to sub-study registration and must not be planning to receive any such agents while on
protocol treatment; however, intranasal and inhaled corticosteroids or systemic
corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
equivalent are allowed

- Patients must not have any prior grade >= 3 immune-related adverse event (irAE) or any
unresolved irAE > grade 1

- Patients must not have any history of organ transplant that requires use of
immunosuppressives

- Patients must not have any known allergy or reaction to any component of the MEDI4736
formulation

- Patients must not have a known history of tuberculosis

- Patients must not have received a live attenuated vaccination within 28 days prior to
sub-study registration

- Patients must not have known human immunodeficiency virus (HIV), hepatitis B or C
positivity

- Patients must also be offered participation in banking for future use of specimens

- STEP 2 TO MEDI4736 RE-TREATMENT REGISTRATION:

- Patient must have progressed following 12 months of treatment with MEDI4736; patients
who discontinue MEDI4736 prior to the completion of 12 months (for any reason) are not
eligible; patients who have already completed two 12-month periods of treatment are
not eligible

- Patients may have measurable or non-measurable disease documented by computed
tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined positron
emission tomography (PET)/CT may be used to document only non-measurable disease
unless it is of diagnostic quality; measurable disease must be assessed within 28 days
prior to re-treatment registration; pleural effusions, ascites and laboratory
parameters are not acceptable as the only evidence of disease; non-measurable disease
must be assessed within 42 days prior to re-treatment registration; all disease must
be assessed and documented on the Baseline Tumor Assessment Form; patients whose only
measurable disease is within a previous radiation therapy port must demonstrate
clearly progressive disease (in the opinion of the treating investigator) prior to
RE-TREATMENT registration

- Patients must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to RE-TREATMENT registration; patient must
not have leptomeningeal disease, spinal cord compression or brain metastases unless:
metastases have been locally treated and have remained clinically controlled and
asymptomatic for at least 14 days following treatment and prior to RE-TREATMENT
registration, AND patient has no residual neurological dysfunction and has been off
corticosteroids for at least 24 hours prior to RE-TREATMENT registration

- Patients must not have received any treatment after discontinuing MEDI4736 with the
following exceptions; localized palliative radiation therapy is allowed for symptom
management, provided and treatment is completed >= 14 days prior to RE-TREATMENT
registration; local treatment for brain metastases is allowed

- Patients must not have received any immunosuppressive medication within 28 days prior
to RE-TREATMENT registration and must not be planning to receive any such agents while
on protocol treatment; however, intranasal and inhaled corticosteroids or systemic
corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or
equivalent are allowed

- Patients must not have any prior grade >= 3 immune-related adverse event (irAE) or any
unresolved irAE > grade 1 (MEDI4736 RE-TREATMENT)

- Patients must not have received a live attenuated vaccination within 28 days prior to
RE-TREATMENT registration

- Patients must not have known HIV, hepatitis B or hepatitis C positivity

- Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment; concurrent use of hormones for
non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement
therapy) is acceptable

- Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to
RE-TREATMENT registration

- Platelet count >= 100,000 mcl obtained within 28 days prior to RE-TREATMENT
registration

- Hemoglobin >= 9 g/dL obtained within 28 days prior to RE-TREATMENT registration

- Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to
RE-TREATMENT registration; for patients with liver metastases, bilirubin must be =< 5
x IULN

- Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
within 28 days prior to RE-TREATMENT registration (if both ALT and AST are done, both
must be =< 2 IULN); for patients with liver metastases, either ALT or AST must be =< 5
x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

- Patients must have a serum creatinine =< the IULN OR measured or calculated creatinine
clearance >= 50 mL/min using the Cockcroft-Gault formula

- Patients must have Zubrod performance status of 0-1 documented within 28 days prior to
RE-TREATMENT registration

- Prestudy history and physical exam must be obtained within 28 days prior to
RE-TREATMENT registration

- Patients must not be pregnant or nursing; women/men of reproductive potential must
have agreed to use an effective contraceptive method; a woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months; in addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures

- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system

- Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines