Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab in Combination With Talazoparib in Patients With SLFN11 Positive Extensive Stage Small Cell Lung Cancer (ES-SCLC)
Overview
- Phase
- Phase 2
- Intervention
- Biopsy Procedure
- Conditions
- Extensive Stage Lung Small Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 103
- Locations
- 1124
- Primary Endpoint
- Progression free survival
- Status
- Active, not recruiting
- Last Updated
- yesterday
Overview
Brief Summary
This phase II trial studies whether atezolizumab in combination with talazoparib works better than atezolizumab alone as maintenance therapy for patients with SLFN11-positive extensive-stage small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair damage to DNA, the genetic material that serves as the body's instruction book. Changes (mutations) in DNA can cause tumor cells to grow quickly and out of control, but PARP inhibitors like talazoparib may keep PARP from working, so tumor cells can't repair themselves, and they stop growing. Giving atezolizumab in combination with talazoparib may help lower the chance of extensive-stage small cell lung cancer growing and spreading compared to atezolizumab alone.
Detailed Description
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. Patients may undergo magnetic resonance imaging (MRI) during screening. Patients undergo tumor biopsy while on study. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study.
Investigators
Eligibility Criteria
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 who have transformed to SCLC from lung non-small cell carcinoma (NSCLC) or have SCLC with mixed histology are not eligible
- •STEP 1: SCREENING REGISTRATION: Participants must have completed at least day 3 of cycle 1 dosing 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 be \>= 18 years of age at the time of Step 1 Screening Registration
- •STEP 1: SCREENING REGISTRATION: Participants must have adequate tumor tissue available from a core biopsy or fine needle aspiration (FNA) defined as:
- •At least two (3-5 microns) (three slides preferred) unstained slides, or;
- •One (3-5 microns) (two slides preferred) unstained slide plus one 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
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Biopsy Procedure
Arm I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Computed Tomography
Arm I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Biospecimen Collection
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Biopsy Procedure
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Computed Tomography
Arm I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Biospecimen Collection
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Talazoparib
Arm I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Atezolizumab
Arm II (atezolizumab, talazoparib)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Progression free survival
Time Frame: From the date of maintenance randomization to the date of first document of progression or symptomatic deterioration, or death due to any cause, assessed up to 18 months
Analysis will be done using a 1-sided 10% level stratified log-rank test. Will be estimated using the Kaplan-Meier method. Associated confidence intervals around the median will be performed using the Brookmeyer-Crowley method.
Secondary Outcomes
- Overall survival(From the date of maintenance randomization until death from any cause, with participants last known to be alive censored at the date of last contact, assessed up to 3 years from randomization)