Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer
Phase 1
Active, not recruiting
- Conditions
- Stage IV Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03559049
- Lead Sponsor
- University of Michigan Rogel Cancer Center
- Brief Summary
This study is a multi-center, Phase I/II, single arm trial to assess the safety and efficacy of the combination of oral rucaparib plus intravenous pembrolizumab as maintenance therapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) without progressive disease (PD), as confirmed on CT scans, after induction therapy with carboplatin/pemetrexed/pembrolizumab (CPP) triplet therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25
Inclusion Criteria
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥18 years of age on day of signing informed consent.
- Have a life expectancy of at least 3 months.
- Have a diagnosis of stage IV non-squamous NSCLC whose tumors do not have an epidermal sensitizing growth factor (EGFR) mutation or BRAF mutation or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1 and have at least one measurable lesion based on RECIST v1.1.
- Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix 15.1).
- Demonstrate adequate organ function
- Female subject of childbearing potential should have a serum pregnancy test within -28 days of enrollment and 72 hours prior to receiving the first dose of study medications.
- Female subjects of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.3.3 for the course of the study through 180 days after the last dose of study medications. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.3.3, starting with the first dose of study therapy through 180 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- If the patient has archival tissue, this should be collected for correlative studies. If archival tissue does not exist, a new biopsy is not required
Exclusion Criteria
- Received previous systemic therapy for stage IV NSCLC
- Received radiation to the lungs >30Gy ≤6 months of enrollment
- Received palliative radiation within 7 days of enrollment
- Had prior treatment with any other anti-PD-1, PD-L1, or PD-L2 agent or an antibody targeting other immune-regulatory receptors or mechanisms
- Received prior treatment with a PARP inhibitor
- Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has active autoimmune disease that has required systemic treatment within the past 2 years
- Subjects requiring daily corticosteroids >10mg of prednisone (or its equivalent) would be excluded from the study.
- Has evidence of interstitial lung disease or a history of non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management
- Has an active infection requiring systemic therapy
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment
- Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment
- Has a known history of active TB (Bacillus Tuberculosis)
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days of enrollment
- A medical condition that requires daily systemic corticosteroids, greater than the equivalent of 10mg of prednisone
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rucaparib and Pembrolizumab Maintenance Pemetrexed All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m\^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle). Rucaparib and Pembrolizumab Maintenance Pembrolizumab All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m\^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle). Rucaparib and Pembrolizumab Maintenance Carboplatin All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m\^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle). Rucaparib and Pembrolizumab Maintenance Rucaparib All patients will receive induction therapy with Pembrolizumab (200mg IV on day 1 of every 21 days), Pemetrexed (500mg/m\^2 IV on day 1 of every 21 days), and Carboplatin (AUC5 IV on day 1 of every 21 days). This will be followed by maintenance therapy with Pembrolizumab (200mg IV on day 1 of every 21 days) and Rucaparib (600mg PO BID days 1-21 of each 21 day cycle).
- Primary Outcome Measures
Name Time Method Median duration of time from start of treatment to time of progression Up to 5 years The primary endpoint is median progression free survival (PFS) which is defined as the median duration of time from the start of treatment to progression. Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
- Secondary Outcome Measures
Name Time Method Median duration of time from the start of treatment until death Up to 5 years The secondary endpoint is median overall survival (OS) which is defined as the median duration of time from the start of treatment until death.
Response rate Up to 5 years Percentage of patients who achieve a complete or partial response after at least one cycle of maintenance therapy with rucaparib and pembrolizumab. Response assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRecist).
Trial Locations
- Locations (3)
The University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States