Current treatment for first-line ES-SCLC includes EP and EP plus PD-L1 antibodies. Although the objective response rate (ORR) is high (around 60-65%), median progression free survival (PFS) remains low (< 6 months), with median overall survival at 10-13 months1,2. Therefore, 1L ES-SCLC remains a serious unmet medical need.
Plinabulin, a potent dendritic cell (DC) maturation agent3, has been studied in a triple combination with various immuno-oncology agents and chemotherapy or radiation, with the potential to enhance the efficacy of PD-1/PD-L1 blockade and restore sensitivity in patients who become resistant [NCT04902040, NCT05599789]. Preliminary re-sensitization data in PD-1/PD-L1 antibody failed patients in 8 cancer types [NCT04902040, IIT at MD Anderson] corresponding response with Plinabulin DC maturation was presented at SITC conference in
This Phase 2 trial will evaluate the efficacy and safety of Pembrolizumab, Plinabulin plus EP in 1L ES-SCLC. The study5 is conducted in
- Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1
- Etoposide 100 mg/m2 IV Q3W on Days 1, 2, and 3
- Carboplatin AUC 5 IV Q3W on Day 1 or Cisplatin 75 mg/m2 IV Q3W on Day 1
- Plinabulin 30mg/m2 IV Q3W on Day 1
“Although the current therapies in first-line ES-SCLC, including PD-L1 antibody and EP combination have had a high ORR, the duration of response is still short with median PFS of < 6 months. KEYNOTE-604 study revealed that 12-month PFS rate in patients with pembrolizumab plus EP is 13.6% vs. 3.1% with placebo plus EP. According to Dr. Mellman’s recent review on cancer immunity cycle6, mature DC is critical for the maintenance of cytotoxic T-cell response against the tumor. By adding Plinabulin, a potent DC maturation agent, to pembrolizumab plus EP, could potentially enable a durable response and improve PFS. This combination study represents an important step forward to address this unmet medical need. I am eager to evaluate this treatment in clinical settings, ensuring that cutting-edge, advanced therapies are translated to cancer care worldwide,” said Dr.
“We are pleased to start this second IIT study with Merck. Our first Merck IIT study initiated in
References:
1. Horn, L., Mansfield, A.S., Szczesna, A., et al. First-line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell
2.
3. Kashyap, A.S., Fernandez-Rodriguez, L., Zhao, Y., et al. GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses. Cell Rep 2019; 28(13): 3367-80.e8.
4. Lin, S.H., Cohen, E., Li, Z., et al 732 Immune activation with plinabulin enhances anti-tumor response combining radiation with immune checkpoint blockade.
5. An Open-Label, Single-Arm, Phase II Study of Pembrolizumab, Plinabulin Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell
6. Mellman, I., Chen, D.S., Powles, T. & Turley, S.J. The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity. 2023; 56(10): 2188-2205.
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