Stage IV Non-small Cell Lung Cancer
Conditions
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.
Interventions
DRUGPembrolizumab
200mg IV every 21 days
DRUGPemetrexed
500mg/m\^2 IV every 21 days
DRUGCarboplatin
AUC 5 IV every 21 days
DRUGRucaparib
600mg PO, BID days 1-21 of each 21 day cycle
Sponsors
University of Michigan Rogel Cancer Center
Merck Sharp & Dohme LLC
Clovis Oncology, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAngel Qin, MD
University of Michigan Rogel Cancer Center
Participant flow
Pre-assignment details
1 patient was deemed an incorrect consent after enrollment and never started on therapy
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 8 / 14 |
Outcome results
None listed