Single arm one stage Phase II study: post 4-6 cycles platinum doublet chemotherapy for patients with metastatic Non Small Cell Lung Cancer (NSCLC) offering Pembrolizumab as maintenance therapy to non-progressors with primary endpoint: Immune Related Progression Free Survival (irPFS) at 1 year. Aim to show that this is at least 25% (compared to an expected 12% 1 year PFS based on the Pemetrexed and Erlotinib maintenance trials).
Rationale: There are currently no data on maintenance therapy with PD1/ PDL1 inhibitors in NSCLC. After an initial response / stable disease to first line chemotherapy, non-progressors / candidates for maintenance treatment, represent an ideal setting / patient group to test the efficacy of Pembrolizumab given that chemotherapy results in antigen release, hence it has the potential to augment immune checkpoint blockade, and following disease cytoreduction, this represents a lower disease burden setting, that may suit checkpoint inhibition better given the recent studies in Prostate cancer with Ipilimumab and Melanoma with Pembrolizumab(suggesting better outcomes for patients with less extensive disease). Primary endpoint: percentage of patients that have not progressed at 1 year using immune related radiological criteria. All patients to be treated with fixed dose 200mg iv Pembrolizumab until unacceptable toxicity, disease progression or completion of 2 years therapy. Statistical Analysis Plan Summary The study employs a one stage phase II Fleming's design using irPFS at 1 year as primary endpoint. Using response hypotheses of H0 \< 12 % and Ha\> 25% i.e. that the irPFS at 1 year for the maintenance Pembrolizumab arm is 25%, compared to 12% in the normal chemotherapy maintenance arm, with a significance level (i.e., the probability of rejecting H0 when it is true) α=0.05 and the power (i.e. the probability of deciding the regimen is active) is 0.8 when true response rate is 25%, 48 patients are required to be entered into this study. Entry Criteria Diagnosis/Condition for Entry into the Trial In order to be eligible for trial entry, patients must have a diagnosis of metastatic Non Small Cell Lung Cancer, and should not have progressed after first line palliative chemotherapy with a platinum doublet. They should have received no more than six (6) cycles of a platinum doublet chemotherapy, and should be able to receive treatment within three (3) to six (6) weeks from the last chemotherapy administration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Switch maintenance pembrolizumab treatment
Bank of Cyprus Oncology Centre
Nicosia, Strovolos, Cyprus
Immune Related Progression Free Survival (irPFS) at 1 Year
To investigate whether treatment with pembrolizumab improves 1 year irPFS, compared to historical controls (from the Pemetrexed and Erlotinib maintenance trials). Aim to show that this is at least 25% (compared to an expected 12% 1 year PFS based on the Pemetrexed and Erlotinib maintenance trials) using a one stage phase II Fleming's design.
Time frame: 4 years
Response Rates Using RECIST Version 1.1
Response rates according to RECIST criteria Version 1.1 where Complete response(CR): Disappearance of all target lesions. Partial response(PR): At least a 30% decrease in the sum of diameters of all target lesions, (from baseline sum of diameters in the absence of CR). Progressive disease(PD): Any new lesion or at least a 20% increase in the sum of diameters of target lesions, (from the smallest sum of diameters at prior timepoints -including baseline). Stable disease(SD): Neither CR or a PR nor sufficient increase to qualify for PD.
Time frame: 7 years
Response Rates With Immune Related Response Criteria (irRC)
Response rates according to RECIST criteria. Time from randomization of the first patient until database cut-off date for the final analysis (Jul 2016 - May 2023; approximately 7 years).
Time frame: 7 years
Radiological Progression Free Survival (PFS) Using RECIST Criteria Version 1.1
PFS calculated using RECIST criteria. RECIST Criteria Version 1.1: Complete response(CR): Disappearance of all target lesions. Partial response(PR): At least a 30% decrease in the sum of diameters of all target lesions, (from baseline sum of diameters in the absence of CR). Progressive disease(PD): Any new lesion or at least a 20% increase in the sum of diameters of target lesions, (from the smallest sum of diameters at prior timepoints -including baseline). Stable disease(SD): Neither CR or a PR nor sufficient increase to qualify for PD. Immune related irPFS calculated using Immune related Response criteria where upon PD there a CT scan would be repeated in 4-6 weeks to exclude pseudoprogression..
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 7 years
Immune-related PFS Using irRC
PFS calculated using RECIST criteria. Immune related irPFS calculated using Immune related Response criteria.
Time frame: 7 years
Overall Survival
Defined as time from the date of randomisation until death from any cause or time to the last follow up appointment (censored).
Time frame: 7 years
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Assessed through analysis of the worst grade of toxicity/adverse events according to CTCAE v4.0 criteria observed over the whole treatment period. Adverse events are collected from study treatment initiation to 30 days after treatment is ceased for any reason. Serious adverse events and events of clinical interest are collected within 90 days after last dose of trial treatment.
Time frame: 7 years