Fase I-II . Lurbinectedin in Combination with Pembrolizumab for Patients with Relapsed Small Cell Lung Cancer. LUPER Clinical Trial .
Small cell lung cancer (SCLC) cells are highly dependent on oncogenic transcription factors (TF) such as ASCL1, NeuroD1 and NFIB, which support their growth. Lurbinectedin is a selective transcription protein-coding gene inhibitor, that causes the detachment of TF from target promoters.
Moreover, in vivo studies have shown lurbinectedin affects the inflammatory microenvironment, by inducing a pro-apoptotic effect on tumor-associated macrophages (TAMs) and a specific inflammatory cytokines inhibition of production.
Lurbinectedin was approved by the FDA for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy based on a single-arm, open-label study phase 2 basket trial..
The aim of this phase I/II study is to assess the safety, tolerability and preliminary efficacy of lurbinectedin in combination with pembrolizumab for the treatment of pts with SCLC in second line after relapse or progressive disease.
The phase I stage is a dose escalation to select the recommended dose (RD) based on the safety observed after the administration of lurbinectedin in combination with pembrolizumab. The phase II stage will explore the clinical activity at the RD.
Methods
This is a multicenter, open-label, single-arm, phase I/II study of lurbinectedin (iv) in combination with pembrolizumab (iv) in pts with relapsed or progressive SCLC (NCT04358237).
In the phase I, cohorts of 3-6 pts with SCLC will be treated with escalating doses of PM01183 in combination with a fixed dose of pembrolizumab. In the phase II stage, a single expansion cohort of approximately 30 pts will be treated with lurbinectedin combined with pembrolizumab at the recommended dose (RD) determined during the phase I stage.
Regardless of stage, pts will receive lurbinectedin in combination with pembrolizumab until progression, unacceptable toxicity, consent withdrawal or if not considered in their best interest to continue.
Main inclusion criteria include: (a) pts with histologically confirmed diagnosis of SCLC whose disease has progressed after first-line chemotherapy-based regimen, (b) at least 4 weeks since the last anticancer therapy, (c) measurable or evaluable disease according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v 1.1).
Primary objectives: (i) the determination of maximum tolerated dose (MTD) and RD, and dose-limiting toxicities (DLTs) of lurbinectedin in combination with pembrolizumab, and (ii) to assess the efficacy of lurbinectedin in combination with pembrolizumab.
Secondary objectives include: (i) to obtain preliminary information on clinical antitumor activity of this combination in pts with SCLC, (ii) to characterize antitumor activity of this combination as per RECIST 1.1 in terms of overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS), (iii) to characterize the safety profile and the plasma pharmacokinetics (PK) of the combination, (iv) to perform pharmacogenetic (PGt) and pharmacogenomic (PGx) analysis in tumor samples of pts. Current status active, not yet recruiting.