Serplulimab: Dosing, Schedule, and Approved Indications
Serplulimab is administered at 3 mg/kg intravenously every 2 weeks for patients with dMMR/MSI-H solid tumors, including advanced colorectal cancer who have failed standard treatment. 1
Approved Indications
Primary Indication: MSI-H/dMMR Solid Tumors
- Serplulimab is approved for adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) solid tumors that have failed to respond to previous standard treatments. 2
- This includes patients with advanced colorectal cancer who have progressed after standard chemotherapy regimens. 1
Colorectal Cancer Specific Indications
- Second-line treatment: For MSI-H/dMMR patients who were not previously treated with immune checkpoint inhibitors in first-line therapy (Category 2A recommendation). 1
- Third-line treatment: For MSI-H/dMMR patients who were previously treated with immune checkpoint inhibitors in first and second lines (Category 2A recommendation). 1
- The Chinese Society of Clinical Oncology (CSCO) prioritizes Chinese-manufactured agents including serplulimab for MSI-H/dMMR advanced colorectal cancer patients. 1
Small Cell Lung Cancer
- Serplulimab is approved for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with carboplatin and etoposide. 1, 3
- In the ASTRUM-005 trial, serplulimab combined with chemotherapy demonstrated median overall survival of 15.4 months versus 10.9 months with chemotherapy alone (HR 0.63, P < .001). 1, 3
Squamous Non-Small Cell Lung Cancer
- Serplulimab 4.5 mg/kg every 3 weeks is used in combination with nab-paclitaxel and carboplatin for first-line treatment of advanced squamous NSCLC without targetable gene alterations. 4
- The ASTRUM-004 trial showed improved median OS (HR 0.73, P = 0.010) with manageable safety profile. 4
Dosing Regimens
Standard Dosing for Solid Tumors
- Dose: 3 mg/kg 1
- Route: Intravenous infusion 1
- Schedule: Day 1, repeat every 2 weeks 1
- Duration: Continue until disease progression or unacceptable toxicity 5
Alternative Dosing for Lung Cancer
- Dose: 4.5 mg/kg 4, 3
- Route: Intravenous infusion 4, 3
- Schedule: Every 3 weeks when combined with chemotherapy 4, 3
- Combination: Given with carboplatin and etoposide (SCLC) or nab-paclitaxel and carboplatin (squamous NSCLC) for up to 4 cycles, followed by maintenance serplulimab. 1, 4, 3
Safety Profile
Common Adverse Events
- Treatment-related adverse events grade ≥3 occurred in 33.2% of patients receiving serplulimab plus chemotherapy versus 27.6% with chemotherapy alone in ES-SCLC. 3
- In the phase I dose-finding study, 75.9% of patients experienced treatment-emergent adverse events related to serplulimab, with nausea being most frequent (24.1%). 5
- Grade ≥3 events occurred in only 13.8% of patients in the phase I study, demonstrating acceptable tolerability. 5
Squamous NSCLC Safety
- Grade ≥3 serplulimab-related adverse events occurred in 35.2% of patients in the ASTRUM-004 trial, with manageable safety profile. 4
Clinical Considerations
Pharmacokinetics
- Serplulimab demonstrates minimal accumulation after repeated administration, with functional PD-1 blockade observed across all dose levels. 5
- The maximum tolerated dose was not reached in phase I studies, supporting the safety of current dosing regimens. 5
Comparative Efficacy
- In real-world data comparing PD-1/PD-L1 inhibitors for ES-SCLC, serplulimab showed median PFS of 6.9 months and median OS of 15.0 months, with no significant differences compared to durvalumab or atezolizumab. 6
- Serplulimab has similar or better affinity and pre-clinical antitumor activity compared to pembrolizumab and nivolumab. 5