Lung-MAP: S1400 Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IIIB-IV Squamous Cell Lung Cancer

This screening and multi-sub-study randomized phase II/III trial will establish a method for
genomic screening of similar large cancer populations followed by assigning and accruing
simultaneously to a multi-sub-study "Master Protocol". The type of cancer trait (biomarker)
will determine to which sub-study, within this protocol, a participant will be assigned to
compare new targeted cancer therapy, designed to block the growth and spread of cancer, or
combinations to standard of care therapy with the ultimate goal of being able to approve new
targeted therapies in this setting. In addition, the protocol includes a "non-match"
sub-study which will include all screened patients not eligible for any of the
biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of
care also with the goal of approval.

Eligibility Criteria

Inclusion Criteria:

- SCREENING REGISTRATION:

- Patients must have pathologically proven squamous cell non-small cell lung cancer
(NSCLC) confirmed by tumor biopsy and/or fine-needle aspiration; disease must be
either advanced, incurable stage IIIB or stage IV NSCLC; the primary diagnosis of
SCCA should be established using the current World Health Organization
(WHO)/International Association for the Study of Lung Cancer (IASLC)-classification
of Thoracic Malignancies; the diagnosis is based on hematoxylin and eosin (H&E)
stained slides with or without specific defined immunohistochemistry (IHC)
characteristic (p40/p63 positive, transcription termination factor [TTF1] negative)
if required for diagnosis; mixed histologies will be allowed provided that they
contain >= 50% of the squamous component

- Patients must have progressed after receiving exactly one front-line platinum
containing metastatic chemotherapy regimen

- Patients must have adequate tumor tissue available (defined as >= 20% tumor cells as
confirmed by the treating institution's local pathologist); patients must agree to
have this tissue submitted to Foundation Medicine for common broad platform Clinical
Laboratory Improvement Amendments (CLIA) biomarker profiling; if archival tumor is
used either a tumor block or at a minimum 12 formalin-fixed paraffin-embedded (FFPE)
slides 4-5 microns thick are required, but 20 slides are strongly recommended; in the
event that patient's archival tumor material is derived from a fine needle aspirate
and the tumor material from fine needle aspirate or from core needle biopsy is
exhausted a new fresh tumor biopsy will be obtained and will be formalin fixed and
paraffin-embedded

- Patients must not have a known epidermal growth factor receptor (EGFR) mutation or
anaplastic lymphoma kinase (ALK) fusion; in addition, patients whose biomarker
profiling results indicate the presence of an EGFR mutation or ALK fusion will be
notified that they are not eligible for any of the sub-studies

- Patients must have Zubrod performance status =< 2 documented within 28 days prior to
screening registration

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

- Patients must be willing to provide prior smoking history

- Patients or their legally authorized representative 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

- 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

- SUB-STUDY ASSIGNMENT:

- Patients whose biomarker profiling results indicate the presence of an EGFR mutation
or echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion are not
eligible

- Patients must be registered to the assigned sub-study within 28 calendar days of
receiving sub-study assignment from the statistical center

- Patients must have 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; if patient has measurable disease it must assessed within 28 days
prior to sub-study treatment arm randomization; 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 registration; all
disease must be assessed and documented on the Baseline Tumor Assessment Form;
patients with active new disease growth in previously irradiated site are eligible

- Patients must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to sub-study treatment arm randomization;
patient must not have leptomeningeal disease, spinal cord compression or brain
metastases unless: (1) metastases have been locally treated and have remained
clinically controlled and asymptomatic for at least 28 days following treatment, AND
(2) patient has no residual neurological dysfunction and has been off corticosteroids
for at least 14 days prior to randomization

- Patients must have progressed after receiving exactly one front-line platinum
containing metastatic chemotherapy regimen; patients must not have received any prior
systemic chemotherapy or investigational drug within 21 days prior to sub-study
treatment arm randomization; patients must have recovered (=< grade 1) from any side
effects of prior therapy; localized palliative radiotherapy >= 14 days is allowed

- Patient must have fully recovered from the effects of prior surgery prior to
sub-study treatment arm randomization

- 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
sub-study treatment arm randomization

- Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study treatment
arm randomization

- Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study treatment arm
randomization

- Serum bilirubin =< 2 X institutional upper limit of normal (IULN) within 28 days
prior to sub-study treatment arm randomization

- Either serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase
[AST]) or serum glutamate pyruvate transferase (SGPT) (alanine aminotransferase
[ALT]) =< 2.5 x IULN within 28 days prior to sub-study treatment arm randomization
(if both SGOT and SGPT are done, both must be =< 2 IULN)

- For patients with liver metastases, bilirubin and either SGOT and SGPT must be =< 5 x
IULN

- Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50
cc/min using the following Cockroft-Gault Formula within 28 days prior to sub-study
treatment arm randomization

- Patients must have Zubrod performance status =< 2 documented within 28 days prior to
sub-study treatment arm randomization

- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, and myocardial infarction
within 6 months, or serious uncontrolled cardiac arrhythmia

- Patients must not have documented evidence of acute hepatitis or have an active or
uncontrolled infection

- Patients must not have a known history of human immunodeficiency virus (HIV)
seropositivity

- Prestudy history and physical must be obtained within 28 days prior to sub-study
treatment arm randomization

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease free for five years

- 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

- S1400A:

- Patients must not have any prior exposure to immunotherapy such as, but not limited
to other anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death
(PD)-1, or anti-PD-L1 antibodies excluding vaccines within 28 days prior to sub-study
treatment arm randomization

- Patients must not have received or be planning to receive any anti-cancer therapy
whether chemotherapy, or biologic therapy, therefore receipt of the last dose of
anti-cancer therapy, (chemotherapy, endocrine therapy, targeted therapy, biologic
therapy, or tumor embolization) > 21 days prior to randomization (> 14 days prior to
randomization for patients who have received prior TKIs [e.g. erlotinib, gefitinib,
or crizotinib] and > 42 days for nitrosoureas or mitomycin-c)

- 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 (eg, insulin for diabetes and hormone replacement
therapy) is acceptable; patients must not have received or be planning to receive any
immunosuppressive medication within 28 days prior to sub-study treatment arm
randomization, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
or equivalent

- 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; Wegner syndrome; Hashimoto
syndrome) within 3 years prior to sub-study treatment arm randomization; patients
with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic
treatment (within the past 3 years) are not excluded

- Patients must not have any history of primary immunodeficiency

- 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 treatment arm randomization

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

- S1400B:

- Hemoglobin A1c (HbA1c) < 7% obtained within 28 days prior to sub-study treatment arm
randomization

- Fasting glucose < 125 mg/dl obtained within 28 days prior to sub-study treatment arm
randomization

- Patients must not have Type 1 or 2 diabetes which requires insulin

- Patients must not have active or a history of small or large intestine inflammation
such as Crohn's disease or ulcerative colitis

- Patients must not require daily supplemental oxygen

- Patients must be able to take oral medications; patients may not have any impairment
of gastrointestinal function or gastrointestinal disease that may significantly alter
the absorption of GDC-0032 (e.g. ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome, or small bowel resection)

- Patients must not be taking, nor plan to take while on protocol treatment and for 14
days post the last dose of study treatment, drugs, herbal supplements or foods that
are known to be strong/moderate cytochrome p450, family 3, subfamily A, polypeptide 4
(CYP3A4) substrates

- Patients must not have received prior treatment of docetaxel as part of frontline
platinum-containing chemotherapy (S1400B)

- S1400C:

- Patients must not be taking within 7 days prior to sub-study treatment arm
randomization, nor plan to take while on protocol treatment, CYP3A4 inhibitors and/or
strong CYP3A4 inducers; moderate inhibitors or inducers of isoenzyme CYP3A4 should be
avoided, but if necessary can be used with caution

- Patients must not be taking within 7 days prior to sub-study treatment arm
randomization, nor plan to take while on protocol treatment drugs that are known to
prolong the QT interval

- Patients must not have QTc > 480msec (based on the mean value of the triplicate
electrocardiograms [ECGs]), family or personal history of long or short QT syndrome,
Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes

- Patients must not have uncontrolled electrolyte disorders which can compound the
effects of a QTc-prolonging drug (eg, hypocalcemia, hypokalemia, hypomagnesemia)

- Patients must be able to take oral medications; patient may not have any impairment
of gastrointestinal function or gastrointestinal disease that may significantly alter
the absorption of palbociclib (e.g. ulcerative disease, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome or small bowel resection)

- Patients must not have received prior treatment of docetaxel as part of frontline
platinum-containing chemotherapy (S1400C)

- S1400D:

- Patients must be >= 25 years of age (skeleton maturation is complete)

- Patients must not be taking, nor plan to take while on protocol treatment and for 14
days after the last dose of study treatment drugs, herbal supplements and/or foods
known to modulate CYP3A4 or cytochrome p450, family 2, subfamily D, polypeptide 6
(CYP2D6) enzyme activity and drugs that are known to be CYP3A4 substrates

- Patients must not have received Nitrosourea or mitomycin C within 42 days prior to
sub-study treatment arm randomization

- Patients must not have had any prior exposure to any agent with FGFR inhibition as
its primary pharmacology

- Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained
from 3 consecutive electrocardiograms (ECGs); any clinically important abnormalities
in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch
block, third degree heart block); nor any factors that increase the risk of QTc
prolongation or risk of arrhythmic events such as heart failure, hypokalemia,
congenital long QT syndrome, family history of long QT syndrome or unexplained sudden
death under 40 years of age or any concomitant medication known to prolong the QT
interval

- Patients must be able to take oral medications; patient may not have any impairment
of gastrointestinal function or gastrointestinal disease that may significantly alter
the absorption of AZD4547 (e.g. ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome or small bowel resection)

- Patients must not have a history of hypersensitivity to active or inactive excipients
of AZD4547 or drugs with a similar chemical structure or class to AZD4547

- Patients

Principal Investigator

Chao Huang

Study Contact

ctnursenav@kumc.edu, 913-945-7552

Estimated Completion Date

Friday, April 1, 2022

ClinicalTrials.gov #

NCT02154490
04/29/2015