PRIMARY OBJECTIVE:
I. To compare progression free survival (PFS) among participants with Schlafen family member
11 (SLFN11) positive extensive stage small cell lung cancer (ES-SCLC) randomized to
atezolizumab or atezolizumab plus talazoparib as maintenance therapy.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between the arms. II. To compare objective response rate
(ORR) among participants with measurable disease between the arms, including complete
response (CR) and partial response (PR) (confirmed and unconfirmed) by Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1.
III. To evaluate the frequency and severity of adverse events within each treatment arm.
TRANSLATIONAL MEDICINE OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE: Patients are screened for SLFN11 biomarker during Step 1: Screening Registration by
submitting tumor tissue to MDACC. Patients with SLFN11 biomarker are registered to Step 2:
Randomization and are randomized to 1 or 2 arms.
ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles
repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib orally
(PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and
at the end of 3 years from randomization.
Inclusion Criteria:
- STEP 1: SCREENING REGISTRATION: Participants must have histologically or
pathologically confirmed diagnosis of extensive stage small cell lung cancer (ES-SCLC)
at the time of protocol entry. Participants with mixed histology are excluded
- STEP 1: SCREENING REGISTRATION: Participants must have completed at least one cycle of
frontline induction treatment with platinum plus etoposide plus atezolizumab prior to
Step 1 Screening Registration. Cycle 1 of frontline induction treatment may or may not
contain atezolizumab
- NOTE: Participants may be screened while receiving consolidation thoracic
radiation or during prophylactic cranial irradiation (PCI) at the time of Step 1
Screening Registration. Participants may or may not receive consolidation
thoracic radiation and/or PCI per the discretion of their treating investigator
- STEP 1: SCREENING REGISTRATION: Participants must not have received any immunotherapy
for SCLC prior to starting the frontline induction treatment for ES-SCLC
- STEP 1: SCREENING REGISTRATION: Participants must not have received any
investigational agent for the treatment of ES-SCLC
- STEP 1: SCREENING REGISTRATION: Participants must have adequate tumor tissue available
from a core biopsy defined as:
- At least two (3-5 microns) unstained slides, or;
- One (3-5 microns) unstained slide plus one hematoxylin and eosin (H&E) stained
slide
- Participants must agree to have this tissue submitted to M.D. Anderson Cancer
Center (MDACC) for SLFN11 immunohistochemistry (IHC) testing. Note: A histologic
review will be performed at MDACC to confirm adequate cellularity for the
testing. If inadequate cellularity, additional unstained slides from the same
participant may be submitted if it doesn't exceed the window of starting
maintenance therapy
- STEP 1: SCREENING REGISTRATION: Participants must be informed of the investigational
nature of this study and must sign and give informed consent in accordance with
institutional and federal guidelines
- STEP 1: SCREENING REGISTRATION: As a part of the Oncology Participant 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
- STEP 1: SCREENING REGISTRATION: Participants 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)
- STEP 2: RANDOMIZATION: Site must have received notification from the SWOG Statistics
and Data Management Center (SDMC) that the participant's tumor sample is SLFN11
positive
- STEP 2: RANDOMIZATION: Participants must have their disease assessed either by
computed tomography (CT) of chest/abdomen/pelvis (with contrast, unless
contraindicated) within 28 days prior to Step 2 Registration or by positron emission
tomography (PET)PET/CT of chest/abdomen/pelvis (with contrast, unless
contraindicated)within 42 days prior to Step 2 Registration. Participants may have a
complete response to induction therapy. All known sites of disease must be assessed
and documented on the Baseline Tumor Assessment Form (RECIST 1.1).
- STEP 2: RANDOMIZATION: Patients must have a CT or magnetic resonance imaging (MRI)
scan of the brain to evaluate for central nervous system (CNS) disease within 42 days
prior to Step 2 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 14 days
following treatment, and prior to Step 2 randomization, AND (2) patient has no
residual neurological dysfunction and has been off corticosteroids for at least 24
hours prior to Step 2 randomization
- STEP 2: RANDOMIZATION: Participants must not have had disease progression based on
post induction imaging in the opinion of treating investigator
- STEP 2: RANDOMIZATION: Participants must be registered to Step 2 Randomization prior
to the start of maintenance atezolizumab
- STEP 2: RANDOMIZATION: Participants must have received no fewer than 2 cycles and no
more than 4 cycles of induction treatment with platinum/etoposide/atezolizumab
- STEP 2: RANDOMIZATION: Participant must not have received radiation treatment (RT) or
prophylactic cranial irradiation (PCI) within 14 days prior to Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants must not be taking strong P-glycoprotein (P-gp)
inhibitors (e.g., dronedarone, quinidine, ranolazine), P-gp inducers (e.g., rifampin),
or breast cancer resistance protein (BCRP) inhibitors (e.g., elacridar) within 7 days
prior to randomization. Participants must not plan to receive the therapies listed
above while on protocol treatment)
- STEP 2: RANDOMIZATION: Participants must not have experienced the following during
induction treatment:
- Any grade 3 or worse immune-related adverse event (irAE) in the opinion of the
treating investigator. Exception: asymptomatic nonbullous/nonexfoliative rash
- Any unresolved grade 2 irAE
- Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1
immunotherapy. Exception to the above: Toxicities of any grade that require
replacement therapy and have stabilized on therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) are allowed
- STEP 2: RANDOMIZATION: History and physical exam must be obtained within 28 days prior
to Step 2 randomization
- STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants
with known history or current symptoms of cardiac disease, or history of treatment
with cardiotoxic agents, must have a clinical risk assessment of cardiac function and
be considered class 2B or better on the New York Heart Association Functional
Classification
- STEP 2: RANDOMIZATION: Participants must have Zubrod performance status 0-2 documented
within 28 days prior to Step 2 Randomization.
- STEP 2: RANDOMIZATION: Leukocytes >= 3,000/mcL (within 28 days prior to Step 2
Randomization)
- STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1,500/mcL (within 28 days prior to
Step 2 Randomization)
- STEP 2: RANDOMIZATION: Platelets >= 100,000/mcL (within 28 days prior to Step 2
Randomization)
- STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN)
(within 28 days prior to Step 2 Randomization)
- STEP 2: RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)
=< 3 x institutional ULN (within 28 days prior to Step 2 Randomization)
- STEP 2: RANDOMIZATION: Creatinine =< institutional ULN OR estimated creatinine
clearance > 30 mL/min (within 28 days prior to Step 2 Randomization)
- STEP 2: RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV)
infection must have undetectable HBV viral load on suppressive therapy within in 6
months prior to Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV)
infection must have been treated and cured. For participants with HCV infection who
are currently on treatment must have an undetectable HCV viral load within in 6 months
prior to Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)
infection must be on effective anti-retroviral therapy and must have undetectable
viral load at their most recent viral load test and within 6 months prior to Step 2
Randomization
- STEP 2: RANDOMIZATION: Participants with known diabetes must not have uncontrolled
diabetes. (Uncontrolled diabetes is defined as glycosylated hemoglobin [HgA1C] > 7%)
- STEP 2: RANDOMIZATION: Participants must be able to swallow capsule whole
- STEP 2: RANDOMIZATION: Participants must not have any known clinically significant
liver disease, including cirrhosis, fatty liver, or inherited liver disease
- STEP 2: RANDOMIZATION: Participants must not have end stage renal or other serious
medical illness that may limit survival or the ability to participate in this study
- STEP 2: RANDOMIZATION: Participants must not have a history of idiopathic pulmonary
fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e.,
bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
- STEP 2: RANDOMIZATION: Participants must not have known active tuberculosis (TB)
- STEP 2: RANDOMIZATION: Participants must not have undergone prior allogeneic bone
marrow transplantation or prior solid organ transplantation
- STEP 2: RANDOMIZATION: Participants must not have history of allergic reaction
attributed to compounds of similar chemical or biological composition to atezolizumab
and/or talazoparib
- STEP 2: RANDOMIZATION: Participants must not have a prior or concurrent malignancy
whose natural history or treatment (in the opinion of the treating physician) has the
potential to interfere with the safety or efficacy assessment of the investigational
regimen
- STEP 2: RANDOMIZATION: Participants must not be on corticosteroids at doses greater
than prednisone 10 mg daily or equivalent within 7 days prior to Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants must not receive any live attenuated vaccines
within 28 days prior to Step 2 Randomization or at any time during the study and until
5 months after the last dose of protocol treatment
- STEP 2: RANDOMIZATION: Participants must not have severe infections in the form of
severe sepsis or septic shock including but not limited to hospitalization for
complications of infection, bacteremia, or severe pneumonia within 14 days prior to
Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants must not be pregnant due to the potential
teratogenic side effects of the protocol treatment. Women of reproductive potential
and men must have agreed to use an effective contraception method for the duration of
protocol treatment, and for 7 months after the last dose of protocol treatment. A
woman is considered to be of "reproductive potential" if she has had a 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 participant 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. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with atezolizumab, breastfeeding must be discontinued prior to
Step 2 Randomization
- STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in
specimen banking. With participant consent, specimens must be collected and submitted
via the SWOG Specimen Tracking System
- STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of
this study and must sign and give informed consent in accordance with institutional
and federal guidelines
- STEP 2: RANDOMIZATION: As a part of the 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
- STEP 2: RANDOMIZATION: Participants 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)
