Toripalimab — a PD-1 inhibitor for multiple solid tumors
- Emmanuel Paredes
- Oct 31
- 6 min read
Toripalimab is a humanized IgG4 monoclonal antibody that blocks programmed cell death protein-1 (PD-1). It is US-FDA approved for selected indications including recurrent/metastatic nasopharyngeal carcinoma (NPC), and China-NMPA approved for urotheliel carcinoma, esophageal squamous cell carcinoma, non-squamous / resectable stage IIIA-IIIB NSCLC, ES-SCLC, renal cell carcinoma, and TNBC.
Mechanism of Action
PD-1 is an inhibitory receptor on activated T cells; binding of PD-L1/PD-L2 to PD-1 reduces T-cell proliferation and cytokine production. Toripalimab binds PD-1 and prevents ligand binding, thereby reactivating anti-tumor T-cell responses. Preclinical models demonstrate tumor growth inhibition after PD-1 blockade.
Pharmacokinetics and Pharmacodynamics
Absorption / Route: Intravenous infusion. Steady-state reached by approximately Week 7 with repeated dosing.
Distribution: Mean volume of distribution at steady state (Vss) ≈ 3.7 L.
Clearance & Half-life: Mean clearance ~14.9 mL/h after first dose and ~9.5 mL/h at steady state. Mean terminal half-life ≈ 10 ± 1.5 days after the first dose and 18 ± 9.4 days at steady state.
Metabolism: Catabolic pathways to small peptides (typical for monoclonal antibodies).
Pharmacodynamics: Toripalimab produces measurable immune activation and objective tumor responses in multiple single-arm and randomized trials; exposure-response relationships are not fully characterized in public sources.
Usual Dosing
Monotherapy (example dosing regimens used in trials / label): 3 mg/kg IV every 2 weeks (q2w) has been used in monotherapy studies.
Combination with chemotherapy (NPC indication): 240 mg IV every 3 weeks (q3w) in combination with cisplatin and gemcitabine — continue until disease progression, unacceptable toxicity, or for up to 24 months per trial protocols and label.
Dosing in Renal and Hepatic Impairment
Renal: No clinically meaningful PK differences observed with mild renal impairment (CLcr 60–89 mL/min); moderate/severe renal impairment not well characterized.
Hepatic: No clinically meaningful PK differences observed with mild hepatic impairment; moderate/severe impairment effects not fully studied. Use with caution and consult local prescribing information.
Administration
Route: Intravenous infusion (refer to label for infusion duration and preparation).
Handling: Store refrigerated, do not freeze, and follow standard monoclonal antibody infusion precautions. Premedication is not routinely required but follow institutional practice. Monitor for infusion-related reactions.
Clinical Efficacy
Selected pivotal data:
Recurrent / metastatic nasopharyngeal carcinoma (RM-NPC) — JUPITER-02 (randomized phase III): Toripalimab + gemcitabine + cisplatin (GP) improved progression-free survival and showed an overall survival benefit compared with GP alone in first-line RM-NPC. The trial demonstrated durable benefit and supported regulatory approvals. Long-term analyses reported improved survival rates at 1–3 years in the toripalimab arm.
Chemorefractory NPC — POLARIS-02 (single-arm phase II): Toripalimab monotherapy in platinum-refractory NPC produced an objective response rate (ORR) ~20.5% with durable responses and favorable median duration of response, supporting its activity in later lines.
Other indications and combinations: Multiple phase I/II and later trials have shown activity across tumor types (melanoma, urothelial carcinoma combinations, HCC, gastric cancer cohorts). Toripalimab combinations with chemotherapy or targeted agents have produced clinically meaningful responses in several settings; regulatory approvals in China reflect broader indication coverage.
Safety Profile
Class effects: Immune-mediated adverse events (irAEs) affecting any organ system (e.g., pneumonitis, hepatitis, colitis, endocrinopathies) can be severe or fatal and require early recognition and management per standard guidelines.
Common adverse events with combination regimens (JUPITER-02 / label data): Nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, and cytopenias—reflecting combination chemotherapy plus PD-1 blockade. Incidence patterns vary by regimen and tumor type.
Grade ≥3 AEs: In JUPITER-02 and pooled safety datasets, grade ≥3 AE rates were substantial (reflecting chemotherapy backbone), but addition of toripalimab did not markedly increase treatment-related fatalities in pooled analyses; label and trial reports emphasize monitoring and management. Discontinuation rates due to AE are reported and must be monitored in practice.
Use in Guidelines / Regulatory Status
Regulatory approvals: Toripalimab (Loqtorzi / Tuoyi) has received approvals in China for
1. Unresectable or metastatic melanoma after failure of standard systemic therapy
2. Locally advanced or metastatic urothelial carcinoma that failed platinum containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum containing chemotherapy
3. Recurrent/metastatic nasopharyngeal carcinoma (“NPC”) after failure of at least two lines of prior systemic therapy
4. First-line for locally recurrent or metastatic NPC
5. First-line for unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma
6. First-line treatment for patients with EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous NSCLC
7. The product in combination with chemotherapy as perioperative treatment and subsequently, monotherapy as adjuvant therapy for the treatment of adult patients with resectable stage IIIA-IIIB NSCLC
8. The product in combination with axitinib for the first-line treatment of patients with medium to high risk unresectable or metastatic renal cell carcinoma
9. The product in combination with etoposidein plus platinum for the first-line treatment of extensivestage small cell lung cancer (ES-SCLC)
10. The product in combination with paclitaxel for injection (albumin-bound) for the first-line treatment of recurrent or metastatic TNBC with a well-validated test to evaluate PD-L1 positive (CPS ≥ 1)
The U.S. FDA approved toripalimab-tpzi (Loqtorzi) for recurrent or metastatic nasopharyngeal carcinoma in 2023.
Guidelines: Integration of toripalimab into practice follows its labeled indications and evolving evidence; in NPC, PD-1 inhibitor + chemotherapy regimens (including toripalimab) are now an accepted first-line option in regions where approved and supported by trial data (e.g., JUPITER-02).
In the NCCN guidelines, toripalimab plus cisplatin + gemcitabine is listed as the only Preferred Category 1 first-line regimen for adults with recurrent/metastatic or locally advanced, unresectable NPC (when surgery/radiation are not curative options). Toripalimab monotherapy is listed as the only preferred subsequent-line treatment for adults with recurrent, unresectable or metastatic NPC after disease progression on a platinum-containing regimen.The guideline update reflects strong evidence (phase 3 JUPITER-02 and phase 2 POLARIS-02 trials) showing improved progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with toripalimab-based therapy in NPC.
Comparison with Other Immune Checkpoint Inhibitors
Different contexts matter. Toripalimab data (JUPITER-02) reflect first-line therapy given with gemcitabine-cisplatin; efficacy gains (PFS/OS/ORR) are therefore for the combination. Pembrolizumab and nivolumab data cited are predominantly single-agent in later lines, so direct numeric comparisons (e.g., ORR or grade-3 AE %) must be interpreted in that context.
Efficacy: Toripalimab + chemo produced large PFS and OS improvements vs chemo alone in the first-line RM-NPC setting; single-agent PD-1 inhibitors (pembrolizumab, nivolumab) show meaningful ORR (~20–25%) in pretreated disease but KEYNOTE-122 did not demonstrate superior OS vs single-agent chemotherapy.
Safety: When an ICI is combined with platinum doublet, grade ≥3 TEAEs are high but largely chemotherapy-related (as in JUPITER-02). Immune-related grade ≥3 AEs are higher with toripalimab combination than placebo (≈9.6% vs 1.4%). Single-agent PD-1 therapy generally has lower rates of grade ≥3 TRAEs (e.g., pembrolizumab ~10% in KEYNOTE-122), though earlier single-arm reports sometimes show higher grade-3 rates depending on definitions and attribution.
Drug (trial / setting) | Key population / line | Key efficacy outcome(s) | Grade ≥3 treatment-related / treatment-emergent AEs (reported) | Primary source |
Toripalimab — JUPITER-02 (randomized phase 3; toripalimab + gemcitabine-cisplatin vs placebo + gem-cis) | First-line recurrent/metastatic NPC (treatment-naïve for advanced disease) | Median PFS: 21.4 vs 8.2 months (HR 0.52). OS improved (HR 0.63); ORR 78.8% vs 67.1%; higher CR rate. Durable responses. | Overall grade ≥3 TEAEs similar between arms (89.7% vs 90.2%). Immune-related grade ≥3 AEs: 9.6% (toripalimab) vs 1.4% (placebo). Note: most grade ≥3 events driven by chemotherapy. | JAMA (JUPITER-02 final analysis). (JAMA Network) |
Pembrolizumab — KEYNOTE-122 (randomized phase 3; pembrolizumab vs single-agent chemotherapy) | Platinum-pretreated recurrent/metastatic NPC (2L+ setting) | No OS benefit vs chemotherapy (median OS 17.2 vs 15.3 mo; HR 0.90; not significant). Modest antitumor activity in earlier phase studies but not superior in this phase 3. | Grade 3–5 treatment-related AEs: 10.3% (pembrolizumab) vs 43.8% (chemotherapy). Treatment-related deaths rare (0.9%). | KEYNOTE-122 final report (Annals of Oncology / trial report). (Annals of Oncology) |
Nivolumab — multicenter phase II (Ma et al., J Clin Oncol) | Recurrent/metastatic NPC (heavily pretreated, single-agent nivolumab) | ORR ≈ 20–21%; 1-yr OS ~59% in the single-agent setting (promising activity vs historical controls). | Reported grade ≥3 AEs possibly related to nivolumab in the range ~20–22% (study-specific; includes immune and non-immune events); most toxicities manageable; no unexpected safety signals. | Ma et al., J Clin Oncol (phase II nivolumab study). (PubMed) |
Conclusion
Toripalimab is a PD-1 monoclonal antibody with demonstrated antitumor activity as monotherapy and in combination with chemotherapy across several solid tumors, with the strongest randomized evidence in nasopharyngeal carcinoma (JUPITER-02). Pharmacokinetic and safety profiles are consistent with other PD-1 inhibitors (long half-life, immune-mediated toxicity risk), while clinical development has expanded its approved indications in China and led to approvals elsewhere for selected indications.
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