Moffitt Cancer Center: Clinical Trial 20098

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Clinical Trial 20098

Cancer Type: Thoracic
Interventions:Alimta (Pemetrexed); Olaparib (Lynparza); Paraplatin (carboplatin); Pembrolizumab (Keytruda); Pemetrexed; carboplatin; cisplatin

Study Type: Treatment
Phase of Study: Phase III
Investigators:

Jhanelle Gray

Call 813-745-6100
or 1-800-679-0775

Overview

Study Title

A Phase 3 Study of Pembrolizumab in Combination with Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants with Metastatic Nonsquamous Non-Small-Cell Lung Cancer

Summary

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, v.s. pembrolizumab plus maintenance pemetrexed for the treatment of nonsquamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).

Objective

Primary Objectives: To compare pembrolizumab plus maintenance olaparib with pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by blinded independent central review (BICR). To compare pembrolizumab plus maintenance olaparib with pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS). Secondary Objectives: To evaluate the safety and tolerability of pembrolizumab plus maintenance olaparib compared to pembrolizumab plus maintenance pemetrexed. To evaluate the change from baseline (at randomization) and the time to true deterioration (TTD) in global health status/quality of life (QoL), cough, chest pain, dyspnea and physical functioning following treatment with pembrolizumab plus maintenance olaparib compared with pembrolizumab plus pemetrexed. Exploratory Objectives: To evaluate pembrolizumab plus maintenance olaparib compared to pembrolizumab plus maintenance pemetrexed with respect to objective response rate (ORR) and duration of response (DOR) assessed according to RECIST 1.1 (Section 4.2.1.1) by BICR. To evaluate the effect of PD-L1 expression levels on the efficacy endpoints of OS and PFS assessed according to RECIST 1.1 (Section 4.2.1.1) by BICR. To evaluate pembrolizumab plus maintenance olaparib compared to pembrolizumab plus maintenance pemetrexed with respect to new anticancer therapy (PFS2), as assessed by the investigator using RECIST 1.1. To evaluate pembrolizumab plus maintenance olaparib compared to pembrolizumab plus pemetrexed with respect to the time to first subsequent anti-cancer therapy (TFST) and the time to second subsequent anti-cancer treatment (TSST). To characterize health utilities using the 5-level version of the European Quality of Life (EuroQoL) 5-dimension Questionnaire (EQ-5D-5L) to generate utility scores for use in economic models. To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab in combination with maintenance olaparib.

Inclusion Criteria

Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC.

Have stage IV nonsquamous NSCLC.

Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated.

Have measurable disease based on RECIST 1.1.

Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated.

Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can start the induction phase. Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time.

Have a life expectancy of at least 3 months.

Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention.

Have not received prior systemic treatment for their advanced/metastatic NSCLC.

Have adequate organ function.

Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards.

Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.

Exclusion Criteria

Has predominantly squamous cell histology NSCLC.

Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.

Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib.

Has an active autoimmune disease that has required systemic treatment in past 2 years.

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.

Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection.

Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment.

Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.

Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).

Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.

Has not completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.