First Line Pembrolizumab, Plinabulin Plus Etoposide and Platinum (EP) for ES-SCLC
Status:
Not yet recruiting
Trial end date:
2025-12-01
Target enrollment:
Participant gender:
Summary
Monoclonal antibodies against programmed death 1 (PD-1) and its ligand PD-L1 have shown
efficacy in patients with ES-SCLC in the monotherapy and combination therapy settings. Up to
now, Atezolizumab and Durvalumab has been approved for first line treatment for ES-SCLC in
China combined with EP or EC. Besides, KEYNOTE-604 study revealed that adding pembrolizumab
to standard first-line EP significantly improves PFS in patients with ES-SCLC and is
associated with durable responses in a subset of patients. 12-m PFS rate were 13.6% with
pembrolizumab plus EP and 3.1% with placebo plus EP. The statistical threshold for declaring
significant prolongation of OS was narrowly missed. Considering sicker pts was enrolled and
the interim analysis was quite often, even though the investigators narrowly missed the OS
endpoint, longer numerical OS data was observed. The latest version of NCCN SCLC guidelines
still recommended pembrolizumab as an option for ES-SCLC patients.
Plinabulin received breakthrough designation from both US and China FDA for CIN (Chemotherapy
Induced Neutropenia) prevention indication. As a "pipeline in a drug," plinabulin is being
broadly studied in combination with various immuno-oncology agents that could boost the
effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients.
In a poster released at 2021 ASCO conference, a phase I trial of Plinabulin in combination
with nivolumab and ipilimumab in patients with relapsed small cell lung cancer: Big Ten
Center Research Consortium (BTCRC-LUN17-127) study. Plinabulin in combination with nivolumab
and ipilimumab was safe and well tolerated with promising efficacy signal of 46% ORR.
From above, Pembrolizumab, Plinabulin plus Etoposide and Platinum as First-Line Therapy for
ES-SCLC should be a promising combination therapy, as the investigators expect increased
efficacy and reduced toxicity with the addition of Plinabulin. In this proof of concept phase
II study, the investigators will investigate that the efficacy and safety of Pembrolizumab,
Plinabulin plus Etoposide and Platinum as First-Line Therapy for ES-SCLC.