Sintilimab - Asian-optimized PD-1 checkpoint inhibitor by Lilly and Innovent Biologics
- Emmanuel Paredes
- Dec 17, 2025
- 4 min read
Sintilimab is a fully human IgG4 monoclonal antibody targeting programmed death-1 (PD-1). It is co-developed by Innovent Biologics and Eli Lilly, with clinical development specifically optimized for Asian patient populations. Sintilimab is approved by the National Medical Products Administration (NMPA) of China for multiple solid tumors and hematologic malignancies.
Mechanism of Action
Sintilimab binds to PD-1 on activated T cells, blocking interaction with PD-L1 and PD-L2. This releases immune checkpoint–mediated inhibition, restoring antitumor T-cell activity. Preclinical studies demonstrate high PD-1 receptor occupancy and slow dissociation kinetics, supporting sustained immune activation.
Pharmacokinetics and Pharmacodynamics
Type: Fully human monoclonal antibody (IgG4)
Administration: Intravenous
Half-life: Approximately 20 days
Receptor occupancy: Near-complete PD-1 saturation at standard dosing
Immunogenicity: Low incidence of anti-drug antibodies reported
Usual Dosing
Standard dose: 200 mg IV every 3 weeks
Weight-based dosing (3 mg/kg) has been used in earlier trials but fixed dosing is now standard.
Dosing in Renal and Hepatic Impairment
Renal impairment: No dose adjustment recommended
Mild hepatic impairment: No adjustment required
Moderate to severe hepatic impairment: Limited data; use with caution (Consistent with other PD-1 inhibitors)
Administration
Administered as an IV infusion every 3 weeks
Can be given as monotherapy or in combination with chemotherapy and/or bevacizumab depending on indication
Clinical Efficacy
Indication | Trial | Treatment Arms | Key Efficacy Outcomes | Safety (≥ Grade 3 AEs) | Key Notes | Publication |
NSCLC (Non-squamous, 1L) | ORIENT-11 | Sintilimab + platinum-based chemotherapy vs chemotherapy alone | Median PFS: ~9.2–9.7 vs ~5.0 months OS: ~35–40% reduction in risk of death 2-yr OS rate: ~50% | Not specifically highlighted; consistent with PD-1 + chemo | Outcomes numerically comparable to KEYNOTE-189 despite exclusively Asian population and poorer baseline PS | |
EGFR-mutant NSCLC (post-TKI) | ORIENT-31 | Sintilimab + bevacizumab + chemotherapy | Median PFS: ~7.2 months Risk of progression reduction: ~49% | Acceptable and manageable | First global Phase III study demonstrating benefit of IO-based quadruple therapy in EGFR-TKI–resistant disease | |
Hepatocellular Carcinoma (1L) | ORIENT-32 | Sintilimab + bevacizumab biosimilar vs sorafenib | Median OS: Not reached vs 10.4 months Death risk reduction: 43% Median PFS: 4.6 vs 2.8 months | ~34% (lower than many IO+TKI regimens) | >94% HBV-positive patients; highly relevant to Asian practice | |
Gastric / GEJ Cancer (1L) | ORIENT-16 | Sintilimab + XELOX vs XELOX | Median OS: • CPS ≥5: ~19.2 months • All patients: ~15.2 months Median PFS: ~7.1 months 2-yr PFS rate: ~22.8% | Consistent with PD-1 + chemotherapy | Broad benefit across biomarker subgroups |
Safety Profile
Across studies, sintilimab demonstrates a safety profile consistent with PD-1 inhibitors, with:
Common AEs: Fatigue, rash, pruritus, hypothyroidism
Grade ≥3 TRAEs: Generally ~30–35% in combination regimens
Immune-related AEs: Mostly manageable with standard algorithms
Lower high-grade toxicity rates reported in ORIENT-32 compared with several IO+TKI regimens (cross-trial)
Comparison With Other PD-1 Inhibitors (Contextual, Non–Head-to-Head)
Sintilimab vs Pembrolizumab and Tislelizumab
Efficacy:
Sintilimab demonstrates PFS and OS outcomes numerically comparable to pembrolizumab across multiple tumor types.
Particularly strong results in HBV-associated HCC and EGFR-TKI–resistant NSCLC, populations under-represented in Western trials.
In EGFR-mutant NSCLC, Sintilimab uniquely shows Phase III benefit, where pembrolizumab and tislelizumab lack positive data.
Safety:
Sintilimab shows lower ≥Grade 3 toxicity in combination regimens (notably in HCC) compared with IO+TKI strategies.
Safety is generally comparable or favorable versus tislelizumab in immune-related AE profiles.
Population fit:
Sintilimab trials consistently enroll Asian-dominant or Asian-exclusive populations, enhancing applicability in HBV-prevalent and EGFR-mutant populations.
Important: No direct head-to-head randomized trials exist; comparisons should be interpreted cautiously.
Indication / Setting | Drug | Key Trial | Regimen | Median PFS (mo) | Median OS (mo) | HR for OS | ≥ Grade 3 AEs | Key Contextual Notes |
1L Non-squamous NSCLC | Sintilimab | ORIENT-11 | PD-1 + platinum chemo | ~9.2–9.7 | NR | ~0.60–0.65 | ~60–65% | Exclusively Asian population; worse baseline PS; numerically comparable to KEYNOTE-189 |
Pembrolizumab | KEYNOTE-189 | PD-1 + platinum chemo | 8.8 | 22.0 | 0.56 | ~67% | Global trial; established standard of care | |
Tislelizumab | RATIONALE-304 | PD-1 + platinum chemo | ~9.7 | NR | ~0.64 | ~64% | Asian population; similar efficacy but higher immune-related AEs in some analyses | |
EGFR-mutant NSCLC (post-TKI) | Sintilimab | ORIENT-31 | PD-1 + bevacizumab + chemo | ~7.2 | NR | ~0.51 (PFS) | ~58% | First Phase III positive IO-based quadruple regimen |
Pembrolizumab | — | — | — | — | — | — | No positive Phase III data in EGFR-TKI–resistant setting | |
Tislelizumab | — | — | — | — | — | — | No established Phase III evidence | |
HCC (1L) | Sintilimab | ORIENT-32 | PD-1 + bevacizumab biosimilar | NR | NR | 0.57 | ~34% | Lower ≥G3 toxicity vs IO+TKI regimens; >94% HBV |
Pembrolizumab | KEYNOTE-240 | PD-1 monotherapy | 3.0 | 13.9 | 0.78 | ~62% | Did not meet primary OS endpoint | |
Tislelizumab | RATIONALE-301 | PD-1 monotherapy vs sorafenib | 3.6 | 15.9 | 0.85 (non-inferior) | ~40% | Non-inferior, not superior | |
Gastric / GEJ Cancer (1L) | Sintilimab | ORIENT-16 | PD-1 + XELOX | ~7.1 | ~15.2 (all) | ~0.77 | ~60% | Broad benefit including CPS <5 |
Pembrolizumab | KEYNOTE-859 | PD-1 + chemo | ~6.3 | ~12.9 | ~0.78 | ~65% | Global population | |
Tislelizumab | RATIONALE-305 | PD-1 + chemo | ~6.5 | ~15.0 | ~0.80 | ~63% | Similar efficacy; slightly higher irAE signals |
Sintilimab and tislelizumab show numerically similar PFS, both slightly higher than pembrolizumab in the cross-trial context.
Pembrolizumab shows a longer median OS, reflecting differences in trial populations and disease settings rather than direct superiority.
Sintilimab and tislelizumab demonstrate comparable OS outcomes in predominantly Asian populations.
Sintilimab demonstrates a numerically lower rate of grade ≥3 AEs compared with pembrolizumab and slightly lower than tislelizumab, supporting a favorable tolerability profile.
Important caveat: These graphs are cross-trial, contextual comparisons, not head-to-head analyses. Differences reflect trial design, patient populations (Asian vs global), PD-L1 enrichment, backbone chemotherapy, and follow-up duration. They should be interpreted as illustrative, not definitive comparative efficacy claims.
Regulatory and Guideline Status
Approved by NMPA (China) for NSCLC, HCC, gastric cancer, and other indications
Included in Chinese national treatment guidelines and reimbursement lists
Not US FDA-approved yet, but efficacy and safety data are published in high-impact international journals, including:
The Lancet Oncology
The Lancet Respiratory Medicine
Journal of Thoracic Oncology
Cost and Accessibility
Significantly more affordable than other PD-1 inhibitors
Included in China’s National Reimbursement Drug List (NRDL)
Substantially improves treatment access without compromising efficacy
Conclusions
Sintilimab is a well-validated PD-1 inhibitor with robust phase III evidence, developed specifically for Asian populations and supported by publications in top-tier international journals. While not US FDA-approved yet, its efficacy, safety, and affordability make it a cornerstone immunotherapy in China, with outcomes that compare favorably to globally used PD-1 inhibitors in cross-trial analyses.
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