Randomized Phase II, Open-label Efficacy and Safety Study of Second-line Durvalumab Plus Tremelimumab Versus Platinum-based Chemotherapy Alone in Patients With NSCLC and First-line Checkpoint-inhibitor Therapy (Re-Check)
This is an open label, randomized, Phase II multicenter study designed to evaluate the safety
and efficacy of two different second-line strategies: After failure of first line
mono-immunotherapy with checkpoint inhibitors (anti-PD-1/PD-L1), and subsequent 2 cycles of
standard of care platinum-based chemotherapy, 2 treatment arms will be compared: Arm A
(Experimental Arm): After randomization, patients will receive a combination regimen
featuring a single, priming dose of tremelimumab together with conventional durvalumab
dosing. Durvalumab maintenance therapy will subsequently be continued as study treatment for
up to 12 cycles.
Arm B: After randomization, patients will continue to receive another 2-4 cycles of
platinum-based chemotherapy. Afterwards, patients will end treatment or receive maintenance
pemetrexed therapy as per marketing authorization (depending on histology, maximum of 13
cycles) at the discretion of the investigator
Patients without progression after two cycles of chemotherapy (induction treatment phase)
will be randomized at a 1:1 ratio into one of 2 treatment arms (combination treatment phase).
PD-L1 expression status will be evaluated based on available data. To better focus on
patients with expected good clinical benefit from immunomodulating agents, only patients with
checkpoint-inhibitor treatment as first-line monotherapy and a progression-free survival of
at least 12 weeks will enter the study (at least two re-assessments after initiation of
first-line treatment). Consequently, patients with disease progression as best response of
first-line therapy cannot enter this study. Directly re-challenging patients with anti-PD-L1
and anti-CTLA agents after disease progression on checkpoint-inhibitor monotherapy will be
avoided by the previous application of two cycles of platinum-based chemotherapy as induction
treatment, which may also enhance the antigen release from tumor cells and may further
support the subsequent immunotherapy.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.