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

Sponsor

University of Michigan Rogel Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03559049

Collaborator

Merck Sharp & Dohme LLC (Industry), Clovis Oncology, Inc. (Industry)

Enrollment

Locations

Arm

102.2

Anticipated Duration (Months)

18.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Non-small Cell Lung Cancer	Drug: Pembrolizumab Drug: Pemetrexed Drug: Carboplatin Drug: Rucaparib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 24, 2018

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rucaparib and Pembrolizumab Maintenance 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 200mg IV every 21 days Drug: Pemetrexed 500mg/m^2 IV every 21 days Drug: Carboplatin AUC 5 IV every 21 days Drug: Rucaparib 600mg PO, BID days 1-21 of each 21 day cycle

Arm

Intervention/Treatment

Experimental: Rucaparib and Pembrolizumab Maintenance

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

200mg IV every 21 days

Drug: Pemetrexed

500mg/m^2 IV every 21 days

Drug: Carboplatin

AUC 5 IV every 21 days

Drug: Rucaparib

600mg PO, BID days 1-21 of each 21 day cycle

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	United States	48109
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210