First Line Pembrolizumab, Plinabulin Plus Etoposide and Platinum (EP) for ES-SCLC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorXiaorong Dong
About this trial
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.
Eligibility criteria
Qualifiers
Have a documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration of a defined lesion.
Have extensive stage disease defined as Stage IV (T any, N any, M 1a/b) by the American Joint Committee on Cancer, Eighth Edition.
Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology review.
Life expectancy ≥3 months.
Disqualifiers
Has received prior systemic therapy for the treatment of SCLC.
Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem.
Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study.
Trial design
Treatments tested in this trial
- Pembrolizumab, Plinabulin plus Etoposide and Platinum
Treatment groups
45 Participants
are divided into 1 treatment groupSponsors and collaborators
Xiaorong Dong
Lead sponsor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Sponsor institution
Source ClinicalTrials.gov