An Open-Label, Single-Arm, Phase II Study of Pembrolizumab, Plinabulin Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer
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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Male/female participants who are at least 18 years of age on the day of signing informed consent.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have adequate organ function.
• Criteria for known Hepatitis B and C positive subjects 9.1 Hepatitis B positive subjects
‣ Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment.
⁃ Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
‣ 2 Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to the first treatment.
⁃ Male participants:
⁃ A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
⁃ A female participant is eligible to participate if she is not pregnant, not breastfeeding.