Abstract 106TiP
Background
Since 2015, immune checkpoint inhibitors (ICI) have really improved treatment for advanced lung cancer. One such drug is pembrolizumab that has been initially developped at 2 mg/kg and then moved to a flat dose of 200 mg each 3 weeks (Q3W), which correspond approximatively in European patients to 3 mg/kg. There are several arguments in favor of equivalent ICI activity with a spacing of the intervals between 2 infusions (i.e. pembrolizumab 200 mg each 6 weeks (Q6W)), despite a reduced dose/intensity: 1) it has not been demonstrated that permanent blocking of immune control points is necessary to obtain a prolonged response, 2) the 27 days half-live of pembrolizumab allows consideration of intervals greater than 3 weeks between infusions, assuming that there is no minimum effective serum dose described for these antibodies, 3) larger infusion interval might improve the patient's quality of life (QoL) by reducing the hospitalization time (when pemetrexed is discontinued for toxicity and pembrolizumab continued as a single agent), 4) a substantial economic gain is possible, with a major budget impact at the nationwide.
Trial design
This multicentric randomized study assessing a new mode of ICI administration based on increased interval time between 2 infusions as maintenance treatment in patients with non-squamous non-small cell lung cancer (pembrolizumab 200 mg Q6W, PULSE arm) compared with the Standard of Care (pembrolizumab 200 mg Q3W, SoC arm) on overall survival (OS). Randomization (1:1) is stratified on gender, maintenance treatment and PD-L1 status. Median OS is assumed to be 22months in patients treated by SoC without progression during induction. The efficacy in the PULSE arm is expected to be similar to the one in the SoC arm with a median OS < 17.1months considered unacceptable (non-inferiority limit). Inclusion of 1108 patients is required to observe an HR of at most 1.25 with an interim analysis at mi-accrual (664 events, one-sided α=2.5%, power=80%). With 5% of non-usable data, 1166 patients should be randomized. The inclusions started since March 2023. This study also assess the toxicity, the pharmacokinetic parameters of pembrolizumab, saturation of the target on circulating lymphocytes, the QoL and economic impact.
Clinical trial identification
EudraCT 2021-006795-16; NCT05692999.
Editorial acknowledgement
N. Cozic - Gustave Roussy.
Legal entity responsible for the study
Gustave Roussy, Villejuif, France.
Funding
PULSE trial is expected in - France: a national grant is obtained from the Hospital Clinical Research Program - Spain and France: a binational grant is obtained from Cancer Research Innovation in Science (CRIS) - Belgium: a grant from the KCE Trials Prioritisation Group is pending.
Disclosure
All authors have declared no conflicts of interest.