Lung-MAP: Taselisib as Therapy in Treating Patients With Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

PRIMARY OBJECTIVES:

I. Phase II Component: To evaluate if there is sufficient evidence to continue to the phase
III component by evaluating the objective response rate (ORR) for PI3K Genentech
(GNE)-positive patients registered to S1400B treated with GDC-0032. (Phase II)

II. Phase III Component: If the study meets the criteria specified in S1400, the study will
be amended to include a follow-on randomized phase III trial.

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival
(OS) in both the subset of patients defined to be PI3K GNE-positive and in the entire S1400B
(PI3K Foundation Medicine [FMI] positive) study population treated with GDC-0032. (Phase II)

II. To evaluate ORR in the entire S1400B (PI3K FMI positive) study population treated with
GDC-0032 to evaluate the duration of response (DoR) both in GNE positive and FMI positive.
(Phase II)

III. To evaluate the DoR both in the entire S1400B PI3K FMI positive study population and in
GNE positive patients treated with GDC-0032 who achieve a complete response (CR) or partial
response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria In Solid Tumors
(RECIST) 1.1. (Phase II)

IV. To evaluate the frequency and severity of toxicities associated with GDC-0032. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or
define resistance to the GDC-0032 beyond the chosen biomarker for biomarker-driven
sub-studies.

II. To identify potential resistance biomarkers at disease progression.

III. To establish a tissue/ blood repository from patients with refractory squamous cell
carcinoma (SCCA) of the lung.

OUTLINE: As of 12/18/2015, patients are assigned to Arm I.

ARM I: Patients receive taselisib orally (PO) daily on days 1-21. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day
1. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity. Upon progression, patients may be eligible to re-register to Arm III.

Re-registration ARM III: Patients in Arm II eligible for re-registration receive taselisib
orally (PO) on days 1-21. Courses repeat every 21 days 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 be assigned to S1400B

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

- Fasting glucose < 125 mg/dL obtained within 28 days prior to sub-study registration

- Patients must not have type I or II diabetes that requires anti-hyperglycemic
medication

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

- STEP 2 TO GDC-0032 RE-REGISTRATION:

- Patients must have progressed on arm 2 (docetaxel) of this sub-study

- Patients must not have received any prior systemic therapy (systemic chemotherapy,
immunotherapy or investigational drug) within 21 days prior to step 2 re-registration;
patients must have recovered (< grade 1) from any side effects of prior therapy

- Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI); the CT from a combined 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 step 2 re-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 step 2
re-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 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 step 2 re-registration; 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 14 days following treatment, AND (2) patient has no residual
neurological dysfunction and has been off corticosteroids for at least 1 day prior to
re-registration

- 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 step 2
re-registration

- Platelet count >= 100,000 mcl obtained within 28 days prior to step 2 re-registration

- Hemoglobin >= 9 g/dL obtained within 28 days prior to step 2 re-registration

- Serum bilirubin =< institutional upper limit of normal (IULN); for patients with liver
metastases, bilirubin must be =< 5 x IULN obtained within 28 days prior to step 2
re-registration

- Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
within 28 days prior to step 2 re-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)

- HbA1c < 7% obtained within 28 days prior to step 2 re-registration

- Fasting glucose < 125 mg/dL obtained within 28 days prior to step 2 re-registration

- Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50
mL/min

- Patients must have Zubrod performance status of 0-1 documented within 28 days prior to
step 2 re-registration

- 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 with a known history of human immunodeficiency virus (HIV) seropositivity:
must have undetectable viral load using standard HIV assays in clinical practice; must
have cluster of differentiation (CD)4 count >= 400/mcL; must not require prophylaxis
for any opportunistic infections (i.e., fungal, mycobacterium avium complex [mAC], or
pneumocystis pneumonia [PCP] prophylaxis); must not be newly diagnosed within 12
months prior to re-registration

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

- 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

- 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