At a glance: The KEYNOTE lung cancer trials
The PD-1 inhibitor pembrolizumab is being investigated in multiple KEYNOTE trials across different tumor types, either alone or as part of various combinations, leading to a prodigious amount of information.
Here we provide a quick guide to the 11 non-small-cell lung cancer (NSCLC) trials, all of which are sponsored by the drug manufacturer, Merck Sharp & Dohme. Where a trial comprises multiple solid tumor cohorts, we focus on just the NSCLC cohort in this guide.
Patient population: locally advanced or metastatic NSCLC with PD-L1 positivity
The results of the NSCLC cohort of the KEYNOTE-001 trial were published in The New England Journal of Medicine in May 2015. They showed that pembrolizumab given at a dose of 2 or 10 mg/kg every 3 weeks or 10 mg/kg every 2 weeks was well tolerated and had antitumor activity regardless of whether patients had received prior therapy or not.
Overall survival (OS) data on the treatment-naïve participants of the same trial, published in the Annals of Oncology in April 2017, showed a median OS time of 22.1 months, with greater benefits for those with a PD-L1 tumor proportion score of at least 50%.
Patient population: previously treated advanced NSCLC with ≥1% PD-L1-positive tumor cells
As reported in The Lancet in December 2015, median OS was significantly longer with either the 2 or 10 mg/kg dose of pembrolizumab than with docetaxel 75 mg/m2, all given every 3 weeks. The survival benefit was even greater among patients with PD-L1 expression on at least 50% of tumor cells.
The co-primary endpoint of progression-free survival (PFS) did not differ significantly between the pembrolizumab and docetaxel arms in the overall study population, but pembrolizumab-treated participants with high (≥50%) PD-L1 expression did derive a significant PFS benefit relative to those given the taxane.
Patient population: treatment-naïve metastatic NSCLC with ≥50% PD-L1-positive tumor cells
Comparator: investigator’s choice of five platinum-based chemotherapy regimens
A prespecified interim analysis showed that pembrolizumab, administered at a fixed dose of 200 mg every 3 weeks, significantly extended the primary endpoint of PFS relative to chemotherapy. OS was also significantly longer with pembrolizumab, with 80.2% of patients alive at 6 months, compared with 72.4% in the chemotherapy group.
These results were published in The New England Journal of Medicine in November 2016.
Related news stories: KEYNOTE-024 demonstrates pembrolizumab superiority for PD-L1-positive NSCLC
Patient population: treatment-naïve locally advanced or metastatic NSCLC
This is a multicohort study investigating the addition of pembrolizumab to various chemotherapeutic and immunotherapeutic regimens.
The findings of the cohort comparing carboplatin and pemetrexed with or without pembrolizumab were published in The Lancet Oncology in October 2016, and showed a significantly higher objective response rate (ORR) for the pembrolizumab group.
Related news story: Pembrolizumab addition supported in KEYNOTE-021 study
KEYNOTE-025: Completed, not yet published
Patient population: advanced NSCLC with PD-L1 positivity
The study is evaluating overall response rate in patients given pembrolizumab at a dose of 10 mg/kg on the first day of each 21-day cycle for up to 2 years.
KEYNOTE-011: Currently recruiting
Patient population: advanced NSCLC
In this multicohort trial, the researchers are evaluating the safety and tolerability of single-agent pembrolizumab given at three different doses – 2 or 10 mg/kg or 200 mg – and also administered in combination with platinum-based chemotherapy or the CTLA-4 inhibitor ipilimumab.
The study also includes a cohort of patients with advanced solid tumors and another comprising small-cell lung cancer patients with extensive disease.
Patient population: treatment-naïve advanced NSCLC with ≥1% PD-L1-positive tumor cells
Comparator: carboplatin plus paclitaxel or pemetrexed
This is a head-to-head comparison, with OS as the primary endpoint, of pembrolizumab 200 mg every 3 weeks versus carboplatin given alongside either paclitaxel or pemetrexed in the first-line advanced NSCLC setting.
Patient population: treatment-naïve metastatic nonsquamous NSCLC
Comparator: placebo plus platinum-based chemotherapy and pemetrexed
This trial was initiated in response to the encouraging results of the KEYNOTE-021 study. Participants in the experimental arm are receiving pembrolizumab 200 mg every 3 weeks in combination with pemetrexed plus either cisplatin or carboplatin, while the control arm is receiving placebo plus chemotherapy, with a view to assessing PFS.
KEYNOTE-407: Currently recruiting
Patient population: treatment-naïve metastatic squamous NSCLC
Comparator: carboplatin plus paclitaxel or nab-paclitaxel
Study participants will receive carboplatin plus paclitaxel or nab-paclitaxel, with or without pembrolizumab at a dose of 200 mg on the first day of each 21-day cycle, and PFS and OS will be assessed as the co-primary endpoints.
KEYNOTE-091: Currently recruiting
Patient population: early-stage resectable NSCLC
Also known as PEARLS, this trial is exploring treatment with pembrolizumab 200 mg every 3 weeks or placebo in patients with stage IB–IIIA disease who have undergone surgical resection with or without standard adjuvant therapy. The primary endpoint of the trial is disease-free survival.
Patient population: locally advanced or metastatic NSCLC; Chinese
Here the focus is on evaluating the safety, tolerability and pharmacokinetics of three doses of pembrolizumab (2 or 10 mg/kg or 200 mg every 3 weeks) in Chinese patients. Efficacy, as indicated by the ORR, duration of response, PFS, and OS, will be investigated as the secondary endpoint.
Summary of approvals