Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II Multi-site Study of Rucaparib and Pembrolizumab Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer After Initial Therapy With Carboplatin, Pemetrexed, and Pembrolizumab

Conditions
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Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Rucaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a life expectancy of at least 3 months Have a histologically confirmed diagnosis of stage IV non-squamous NSCLC (non-small cell lung cancer) 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 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death) Demonstrate adequate organ function Female subjects of childbearing potential should have a serum pregnancy within 14 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 for the course of the study through 180 days after the last dose of study medications. Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy. Adequate tissue sample for correlative studies 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rucaparib and Pembrolizumab Maintenance<br>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). | Drug: Pembrolizumab<br>* 200mg IV every 21 days<br>Drug: Pemetrexed<br>* 500mg/m^2 IV every 21 days<br>Drug: Carboplatin<br>* AUC 5 IV every 21 days<br>Drug: Rucaparib<br>* 600mg PO, BID days 1-21 of each 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median duration of time from start of treatment to time of progression | 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. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median duration of time from the start of treatment until death | The secondary endpoint is median overall survival (OS) which is defined as the median duration of time from the start of treatment until death. | Up to 5 years | 
| Response rate | 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). | Up to 5 years |