Tislelizumab-jsgr, a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1
Tislelizumab-jsgr is used in combination with platinum-containing chemotherapy for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express programmed death receptor-(ligand) 1 (PD-[L]1) (≥1).1 Tislelizumab-jsgr is also used as a single agent for the treatment of adults with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-[L]1 inhibitor.1
The use of tislelizumab-jsgr in combination with platinum-containing chemotherapy for the first-line treatment of unresectable or metastatic ESCC is based on results from a global, randomized, placebo-controlled, phase 3 study (RATIONALE-306).1, 8 Enrolled patients were ≥18 years of age with histologically confirmed, unresectable, locally advanced, recurrent, or metastatic ESCC not treated with prior systemic therapy and not amenable to definitive therapies such as surgery or radiation.1, 8 Patients were enrolled regardless of their tumor PD-L1 expression status; all patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and measurable or evaluable disease.1, 8 Eligible patients were randomly assigned to receive tislelizumab-jsgr plus investigator's choice of chemotherapy or placebo plus investigator's choice of chemotherapy.1, 8 Tislelizumab-jsgr was administered at a dosage of 200 mg IV once every 3 weeks.1, 8 Chemotherapy doublet options included a platinum agent (cisplatin or oxaliplatin) in combination with a fluropyrimidine (fluorouracil or capecitabine) or paclitaxel.1, 8 Patients were treated until disease progression, unacceptable toxicity, or withdrawal for other reasons.1, 8 Tumor responses were assessed every 6 weeks for the initial 48 weeks, and then every 9 weeks thereafter by CT or MRI.1, 8
The primary efficacy end point was overall survival.1 A total of 649 patients were randomized.1, 8 The median age of patients was 64 years; 87% of patents were male, 75% were Asian, and 86% had metastatic disease at study entry.1, 8 At the data cut-off, the median follow-up in the tislelizumab and placebo groups was 16.3 months and 9.8 months, respectively.8 The median overall survival was 17.2 months in the tislelizumab group versus 10.6 months in the placebo group.8 Tislelizumab plus chemotherapy was also associated with significant improvement in investigator-assessed progression-free survival and objective response.8
Single Agent After Prior Systemic Chemotherapy
The use of tislelizumab-jsgr as a single agent in the treatment of ESCC is based on a randomized, active-controlled, multicenter, open-label, phase 3 study that compared tislelizumab-jsgr to chemotherapy (paclitaxel, docetaxel, or irinotecan) as second-line treatment for advanced or metastatic ESCC in patients who progressed after first-line systemic treatment.1, 4 Patients 18 years of age or older who had tumor progression within 6 months after definitive chemoradiotherapy, neo-adjuvant, or adjuvant therapy were included in the study.4 Patients were enrolled regardless of their tumor PD-L1 expression level; all patients had an ECOG performance status of 0 or 1.1, 2 Patients who had received prior anti-PD-1 or anti-PD-L1 monoclonal antibodies were excluded.2 Eligible patients were randomly assigned to receive tislelizumab-jsgr or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan).1, 4 Tislelizumab-jsgr was administered at a dosage of 200 mg IV once every 3 weeks.1, 4 Paclitaxel was administered at a dosage of 135-175 mg/m2IV once every 3 weeks, or in doses of 80-100 mg/m2once weekly per regional guidelines.1, 4 Docetaxel was administered at a dosage of 70 or 75 mg/m2 IV once every 3 weeks depending on the study location.4 Irinotecan was administered at a dosage of 125 mg/m2 IV on days 1 and 8, every 21 days.1, 4 Patients were treated until disease progression, unacceptable toxicity, or withdrawal for other reasons.1, 4 Tumor responses were assessed using computed tomography or magnetic resonance imaging (MRI) every 6 weeks for 6 months and then every 9 weeks.1, 4
The primary efficacy end point was overall survival in the intent-to-treat (ITT) population.1, 4 A total of 512 patients were included in the efficacy population.1, 4 The median age of patients was 62 years; 84% of patents were male, approximately 80% were Asian, and 95% had metastatic disease at study entry.1, 4 Tislelizumab provided a modest, but statistically significant, improvement in overall survival compared with chemotherapy.2 The median overall survival was 8.6 months in the tislelizumab group versus 6.3 months in the chemotherapy group.1, 4 The survival benefit of tislelizumab versus chemotherapy was observed in all predefined subgroups, including those based on PD-L1 expression status, region, and race.4 The median progression-free survival was 1.6 months in the tislelizumab group versus 2.1 months in the chemotherapy group.1 The objective response rate was 15.2% and 6.6% in the tislelizumab and chemotherapy groups, respectively, and median duration of response was 10.3 and 6.3 months in these respective treatment groups.1
Tislelizumab-jsgr is used in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of adults with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1).1
The current indication for tislelizumab-jsgr in the treatment of gastric cancer is based on a randomized, double-blind, multicenter, placebo-controlled, phase 3 study that evaluated efficacy and safety of tislelizumab plus chemotherapy for primary treatment of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.1, 7 Patients 18 years of age or older with histologically confirmed, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who had not received previous systemic therapy for advanced disease were included in the study, regardless of their tumor PD-L1 expression level.1, 7 PD-L1 status was assessed by the tumor area positivity (TAP) method and combined positive score (CPS).1 If patients received previous neoadjuvant or adjuvant therapy, a disease progression-free interval of at least 6 months was required prior to the study.7 All patients had an ECOG performance status of 0 or 1 and at least one measurable or non-measurable lesion.7
Patients were randomly assigned to receive tislelizumab-jsgr (200 mg IV every 3 weeks) or placebo, both in addition to investigator's choice of chemotherapy (oxaliplatin and capecitabine doublet therapy or cisplatin and 5-fluorouracil doublet therapy) until disease progression or unacceptable toxicity.7 Capecitabine was administered at a dosage of 1000 mg/m2 orally twice daily on days 1-14 for 6 cycles or more and oxaliplatin was administered at a dosage of 130 mg/m2 IV on day 1 for up to 6 cycles; 5-fluorouracil was administered at a dosage of 800 mg/m2 IV on days 1-5 for up to 6 cycles and cisplatin was administered at a dosage of 80 mg/m2 on day 1 for up to 6 cycles.7
Tumor response was assessed by computed tomography or MRI about every 6 weeks during the first 48 weeks of the study and every 9 weeks thereafter.7 The primary efficacy endpoint was overall survival, defined as the time from randomization to death due to any cause, assessed in patients with a PD-L1 TAP score ≥5% (PD-L1 TAP ≥5% population) and in all randomized patients (intention-to-treat [ITT] population).7
A total of 997 patients were randomized in the study.7 Among these patients, 80% had gastric cancer and 20% had gastroesophageal junction adenocarcinoma.7 The median duration of exposure to chemotherapy was similar between the 2 treatment groups (5.9 months for tislelizumab and 5.7 months for placebo).7 The median age of patients was 61 years; 35% were 65 years of age or older, 69% were male, and 75% were Asian.1 Almost all patients had metastatic disease (99%).7 Overall survival was significantly improved in patients who received tislelizumab plus chemotherapy compared to those who received placebo and chemotherapy in the PD-L1 TAP ≥5% population and in the ITT population.1 Improvement in the ITT population was largely attributed to the results observed in the subgroup of patients with PD-L1 ≥1.1 For patients with a PD-L1 TAP score ≥1%, the median overall survival was 15 months in the tislelizumab-jsgr plus chemotherapy group compared with 12.8 months in the placebo plus chemotherapy group.1 For patients with a PD-L1 CPS score ≥1, the median overall survival was 15.1 months in the tislelizumab-jsgr plus chemotherapy group compared with 12.9 months in the placebo plus chemotherapy group.1 Among patients in the PD-L1 TAP ≥1% group, the median progression-free survival was 6.9 months with tislelizumab and 5.9 months with placebo.1 Among patients in the PD-L1 CPS ≥1 group, the median progression-free survival was 7 months with tislelizumab and 6.4 months with placebo.1 Among patients in the PD-L1 TAP ≥1% group, the objective response rate was 48% and 41% in the tislelizumab and placebo groups, respectively, and median duration of response was 8.6 and 7.2 months in these respective treatment groups.1 Among patients in the PD-L1 CPS ≥1 group, the objective response rate was 49% and 42% in the tislelizumab and placebo groups, respectively, and median duration of response was 8.6 and 7.2 months in these respective treatment groups.1
A diagnosis of nasopharyngeal carcinoma occurs in <1 out of 100,000 individuals globally on an annual basis, with an increased incidence observed in Asian countries and males versus females.10001 Risk factors include smoking history, heavy alcohol use, Epstein-Barr virus (EBV) exposure, Asian descent, and a family history of the cancer type.10001 For patients with stage I-IV nonmetastatic disease, high-dose radiation therapy with chemotherapy is the usual initial treatment option.10001 For those with metastatic and recurrent nasopharyngeal carcinoma, treatment options include radiation therapy, surgery, and chemotherapy/immunotherapy.10001 The administration of chemotherapy/immunotherapy is considered if a patient with metastatic or recurrent disease is no longer amenable to surgery or radiation therapy per the National Cancer Institute (NCI).10001
A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial (RATIONALE-309) evaluated the use of tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer†.10002 RATIONALE-309 enrolled adults (18-75 years of age) with treatment-naïve histologically or cytologically confirmed recurrent or metastatic nasopharyngeal cancer regardless of programmed death-ligand 1 (PD-L1) expression.10002 Eligible patients also had ≥1 measurable lesion per RECIST v1.1, an Eastern Cooperative Oncology Group (ECOG) performance status ≤1, life expectancy of ≥12 weeks, and appropriate organ function.10002 A total of 263 patients were randomly assigned to either tislelizumab 200 mg IV (n=131) or matching placebo (n=132) every 3 weeks in combination with gemcitabine 1 g/m2 IV given on Days 1 and 8 and cisplatin 80 mg/m2 on Day 1.10002 Chemotherapy was administered every 3 weeks for 4 to 6 cycles per investigator discretion.10002 Dosage reduction of each chemotherapeutic agent was allowed twice per protocol before discontinuation.10002 Tislelizumab dose reduction was not allowed during the study; however, temporary interruption of therapy due to adverse effects was allowed, with resumption of therapy required within 12 weeks of the last dose.10002 Study treatment continued until disease progression, occurrence of unacceptable toxicity, or patient withdrawal.10002 Per study protocol, patients in the tislelizumab/chemotherapy arm were allowed to continue tislelizumab monotherapy and patients in the chemotherapy alone arm were permitted to switch over to tislelizumab after disease progression.10002 The primary study endpoint was progression-free survival (PFS) in the intention-to-treat (ITT) population as assessed by an independent review committee.10002 Progression-free survival was defined as the time from randomization to the initial objectively documented disease progression or death from any cause, whichever occurred first.10002 Key secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety.10002
Baseline characteristics were comparable between the study groups.10002 The median age of patients was 50 years, 78.3% were male, and the majority were enrolled from China (94.3%).10002 Recurrent disease was present in 62.4% of patients and 32.7% had primary metastatic disease.10002 The median duration of tislelizumab exposure was 35.9 weeks and the median number of tislelizumab treatment cycles was 11.10002 Most patients in both groups had an undifferentiated, non-keratinized histology (74% in the tislelizumab/chemotherapy group and 72% in the placebo/chemotherapy group).10002
At the time of data cutoff for the interim analysis, the median follow-up was 10 months (range: 0.1 to 23.3 months) and 152 PFS events occurred.10002 Additionally, 63 patients in the tislelizumab/chemotherapy arm and 37 patients in the placebo/chemotherapy arm remained on treatment.10002 Results revealed a significantly improved modified PFS with tislelizumab/chemotherapy versus placebo/chemotherapy per independent review committee assessment (9.2 vs. 7.4 months; hazard ratio [HR] 0.52; 95% confidence interval [CI]; 0.38 to 0.73).10002 An investigator assessment of modified PFS was consistent with these results (9.8 vs. 7.6 months; HR 0.54; 95% CI; 0.38 to 0.76).10002 At the time of an updated data cutoff (median follow-up: 15.5 months), modified PFS as assessed by the independent review committee was consistent with the results from the interim analysis (9.6 vs. 7.4 months; HR 0.50; 95% CI; 0.37 to 0.68).10002 A consistent PFS benefit was seen with tislelizumab/chemotherapy in almost all patient subgroups, regardless of liver metastatic status, baseline EBV level, and tumor cell PD-L1 expression level.10002 The ORR was improved with tislelizumab/chemotherapy (69.5% vs. 55.3%); 16% of patients in the tislelizumab/chemotherapy arm versus 6.8% of patients in the placebo/chemotherapy experienced a complete response.10002 Median DOR was prolonged for patients administered tislelizumab/chemotherapy as compared to placebo/chemotherapy (8.5 vs. 6.1 months).10002 Overall survival (OS) was evaluated at the time of the updated data cutoff with 23 fatalities reported in the tislelizumab/chemotherapy arm and 35 in the placebo/chemotherapy arm.10002 The median OS was not reached in the tislelizumab/chemotherapy arm and was 23 months in the placebo/chemotherapy arm.10002
Treatment-emergent adverse events (TEAEs) were common in both groups; all patients in the tislelizumab/chemotherapy arm and 99.2% of patients in the placebo/chemotherapy arm experienced at least 1 TEAE.10002 Permanent discontinuation of therapy due to a TEAE occurred in 13% of patients in the tislelizumab/chemotherapy arm and 9.1% of patients in the placebo/chemotherapy arm.10002 Deaths related to TEAEs occurred in 5 patients in the tislelizumab/chemotherapy group and 2 patients in the placebo/chemotherapy group.10002 One patient in the tislelizumab/chemotherapy group experienced a TEAE (myelodysplastic syndrome) leading to death considered related to tislelizumab.10002 The most frequently occurring immune-mediated TEAE was hypothyroidism (13.7% of patients in the tislelizumab/chemotherapy arm).10002
Based on current evidence, tislelizumab, in combination with gemcitabine and cisplatin, as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma has Level 1 (high strength/quality) evidence supporting its use.10002 This combination results in an improvement in PFS, ORR, and DOR with a tolerable safety profile.10002
Administer tislelizumab-jsgr by IV infusion after dilution.1 Do not administer as an IV push or single bolus injection.1 Administer tislelizumab-jsgr through an IV line with a sterile, nonpyrogenic, low-protein binding, 0.2 or 0.22 micron in-line or add-on filter.1 Flush the IV line at the end of infusion.1
Do not coadminister other drugs through the same infusion line.1
Store unopened vials at 2-8°C in the original carton to protect the drug from light.1 After the drug is diluted, the prepared dose may be stored at room temperature (20-25°C) for up to 4 hours or under refrigeration (2-8°C) for up to 20 hours, including preparation and infusion time; do not freeze the diluted solution.1 If the drug is refrigerated, allow the diluted solution to come to room temperature prior to administration.1 Discard the diluted solution if not used after 4 hours at room temperature or after 20 hours under refrigeration.1
Must dilute the commercially available injection concentrate prior to administration.1 Visually inspect vials of tislelizumab-jsgr solution for particulate matter and discoloration prior to dilution.1 The solution should be clear to slightly opalescent, and colorless to slightly yellow.1
To prepare the solution for infusion, withdraw the required volume of tislelizumab-jsgr from the vial(s).1 Transfer solution into an IV infusion bag containing 0.9% sodium chloride injection to prepare an infusion solution with a final concentration between 2 mg/mL and 5 mg/mL.1 Mix the diluted solution by gentle inversion to avoid foaming or excessive shearing; do not shake.1 Tislelizumab-jsgr vials are for single use only.1 Discard any unused portion left in the vial.1
For the 150 mg and 200 mg doses, the initial infusion should be administered over 60 minutes.1 If tolerated, all subsequent infusions may be administered over 30 minutes.1
For the 300 mg doses, the initial infusion should be administered over 90 minutes.1 If tolerated, the second infusion may be administered over 60 minutes and subsequent infusions may be administered over 30 minutes.1
The recommended adult IV infusion dosage of tislelizumab-jsgr as a single agent or in combination with other therapeutic agents for the treatment of unresectable or metastatic ESCC is 150 mg once every 2 weeks OR 200 mg once every 3 weeks OR 300 mg once every 4 weeks, until disease progression or unacceptable toxicity.1 Refer to the respective prescribing information for dosing information for the drugs administered in combination with tislelizumab-jsgr.1
The recommended adult IV infusion dosage of tislelizumab-jsgr in combination with platinum and fluoropyrimidine-containing chemotherapy for the first line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma is 150 mg once every 2 weeks OR 200 mg once every 3 weeks OR 300 mg once every 4 weeks, until disease progression or unacceptable toxicity.1 Refer to the respective prescribing information for dosing information for the drugs administered in combination with tislelizumab-jsgr.1
When tislelizumab is used in combination with gemcitabine and cisplatin for the treatment of recurrent or metastatic nasopharyngeal carcinoma†, the usual dosage of tislelizumab administered is 200 mg IV every 3 weeks.10002
Dosage Modifications for Adverse Reactions
If immune-mediated adverse effects occur, temporary interruption or discontinuance of therapy may be required (see Table 1).1 In general, withhold tislelizumab-jsgr for severe (grade 3) immune-mediated adverse reactions.1 Permanently discontinue therapy for life-threatening (grade 4) immune-mediated adverse reactions or recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, and in patients who are not able to reduce corticosteroid dosage to ≤10 mg of prednisone daily (or equivalent) within 12 weeks of initiating steroids.1
Adverse Reaction | Dose Modification Based on Severity |
|---|---|
Pneumonitis | Grade 2: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Grade 3 or 4 or recurrent Grade 2: Permanently discontinue |
Colitis | Grade 2 or 3: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Grade 4: Permanently discontinue |
Hepatitis with no tumor involvement of the liver | AST or ALT increases to >3 times and ≤8 times ULN or total bilirubin increases to >1.5 and ≤3 times ULN: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera AST or ALT increase to >8 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue |
Hepatitis with tumor involvement of the liverb | Baseline AST or ALT is >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN or baseline AST or ALT is >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Baseline AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue |
Endocrinopathies | Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity |
Nephritis with renal dysfunction | Grade 2 or 3 increased blood creatinine: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Grade 4 increased blood creatinine: Permanently discontinue |
Exfoliative dermatologic conditions | Grade 3, or suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS): Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Grade 4, or confirmed SJS, TEN, or DRESS: Permanently discontinue |
Myocarditis | Grade 2, 3, or 4: Permanently discontinue |
Neurological toxicities | Grade 2: Withhold therapy until recovery to Grade 0 or 1; may resume after corticosteroid tapera Grade 3 or 4: Permanently discontinue |
Infusion-related reactions | Grade 1: Slow infusion rate by 50% Grade 2: Interrupt infusion; resume infusion if resolved or decreased to Grade 1, and slow rate of infusion by 50% of the previous rate Grade 3 or 4: Permanently discontinue |
aPermanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to <10 mg per day (or equivalent) within 12 weeks of initiating steroids.
bIf AST and ALT are ≤ULN at baseline, withhold or permanently discontinue tislelizumab-jsgr based on recommendations for hepatitis with no liver involvement.
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1, 2
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1, 2
The manufacturer makes no specific dosage recommendations for geriatric patients.1, 2
Immune-mediated Adverse Reactions
Severe and fatal immune-mediated adverse reactions can occur at any time in any organ system or tissue after initiating treatment with an anti-programmed-death receptor-1 (anti-PD-1) or anti-programmed-death ligand-1 (anti-PD-L1) antibody.1 Tislelizumab-jsgr removes inhibition of the immune response; this may break peripheral tolerance and induce immune-mediated adverse reactions.1
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of tislelizumab-jsgr.1 Such reactions generally occur during treatment but may also occur after the drug is discontinued.1 Monitor patients closely for clinical manifestations of immune-mediated adverse reactions.1 Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.1 In cases of suspected immune-mediated adverse reactions, evaluate the patient to exclude alternative etiologies, including infection.1 Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.1
Withhold or permanently discontinue tislelizumab-jsgr depending on severity of the adverse reaction.1 If interruption or discontinuation of therapy is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until toxicity improves to grade 1 or less.1 Upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.1 Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.1 Permanently discontinue tislelizumab-jsgr if there is no partial or complete resolution within 12 weeks of steroid initiation or if the corticosteroid dosage is not able to be decreased to <10 mg of prednisone daily (or equivalent) within 12 weeks of steroid initiation.1
The immune-mediated adverse reactions described in the following sections may not be inclusive of all possible severe and fatal immune-mediated reactions.1 Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below.1
Tislelizumab-jsgr can cause immune-mediated pneumonitis, which can be fatal.1 In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.1
Immune-mediated pneumonitis occurred in 4.7% (113/2390) of patients receiving tislelizumab-jsgr, including fatal (0.1%), grade 4 (0.3%), grade 3 (1.4%), and grade 2 (1.9%) adverse reactions.1 Permanent discontinuation of tislelizumab-jsgr therapy was required for pneumonitis in 44 patients (1.8%) and the drug was withheld in 40 patients (1.7%).1
Among patients who experienced immune-mediated pneumonitis, 71.7% received systemic corticosteroids and 65.5% received high-dose systemic corticosteroids. 1 Immune-mediated pneumonitis resolved in 48.7% of patients.1 Twenty-six patients reinitiated the drug after symptom improvement; of these, 5 patients had recurrence of pneumonitis.1
Depending on the severity, interrupt or discontinue tislelizumab-jsgr therapy.1
Tislelizumab-jsgr can cause immune-mediated colitis, which can be fatal.1 Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies.1 In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.1
Immune-mediated colitis occurred in 0.8% (19/2390) of patients receiving tislelizumab-jsgr, including grade 3 (0.3%) and grade 2 (0.4%) adverse reactions.1 Colitis led to permanent discontinuation of tislelizumab-jsgr in 5 patients (0.2%) and withholding of the drug in 10 patients (0.4%).1 Among the patients who experienced immune-mediated colitis, 89.5% received systemic corticosteroids, 63.2% received high-dose systemic corticosteroids, and 10.5% received immunosuppressive treatment.1 Immune-mediated colitis resolved in the majority (93.8%) of patients.1 Nine patients reinitiated the drug after symptom improvement; of these, 2 had recurrence of colitis.1
Depending on the severity, interrupt or discontinue tislelizumab-jsgr therapy.1
Tislelizumab-jsgr can cause immune-mediated hepatitis, which can be fatal.1
Immune-mediated hepatitis occurred in 1.3% (30/2390) of patients receiving tislelizumab-jsgr, including grade 4 (0.3%), grade 3 (0.6%), and grade 2 (0.3%) adverse reactions.1 Immune-mediated hepatitis led to permanent discontinuation in 6 patients (0.3%) and withholding of the drug in 19 patients (0.8%).1 Among patients who experienced immune-mediated hepatitis, 83.3% received systemic corticosteroids, 80% received high-dose systemic corticosteroids, and 6.7% received immunosuppressive treatment.1 Immune-mediated hepatitis resolved in 66.7% of patients.1 Of the 19 patients in whom tislelizumab-jsgr was withheld for hepatitis, 7 reinitiated the drug after symptom improvement and 1 had a recurrence of hepatitis.1
Depending on the severity, interrupt or discontinue tislelizumab-jsgr therapy.1
Tislelizumab-jsgr can cause immune-mediated adrenal insufficiency.1 Immune-mediated adrenal insufficiency occurred in 0.5% (12/2390) of patients receiving tislelizumab-jsgr, including grade 4 (0.04%), grade 3 (0.2%), and grade 2 (0.3%) adverse reactions.1 Adrenal insufficiency did not lead to permanent discontinuation of tislelizumab-jsgr.1 Tislelizumab-jsgr was withheld in 10 patients.1 All 12 patients received systemic corticosteroids, and 3 received high-dose systemic corticosteroids.1 Adrenal insufficiency resolved in 25% of the 12 patients.1 Of the 10 patients in whom tislelizumab-jsgr was withheld for adrenal insufficiency, 8 reinitiated the drug after symptom improvement and none experienced recurrence of adrenal insufficiency.1 If grade 2 or higher adrenal insufficiency occurs during tislelizumab-jsgr therapy, initiate symptomatic treatment, including hormone replacement as clinically indicated.1
Tislelizumab-jsgr can also cause immune-mediated hypophysitis, which may present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects.1 Hypophysitis can lead to hypopituitarism.1 If hypophysitis occurs, initiate hormone replacement as clinically indicated.1 Withhold or permanently discontinue tislelizumab-jsgr depending on severity.1 Hypophysitis/hypopituitarism occurred in 0.3% (6/2390) of patients receiving tislelizumab-jsgr, all grade 2 adverse reactions.1 Hypophysitis did not lead to permanent discontinuation in any patient, while treatment was withheld in 1 patient.1 Among the patients who experienced hypophysitis, 83.3% received systemic corticosteroids and 17% received high-dose systemic corticosteroids.1 There was no recurrence of hypophysitis/hypopituitarism in the patient for whom therapy was withheld.1
Tislelizumab-jsgr can cause immune-mediated thyroid disorders.1 Thyroiditis can present with or without endocrinopathy.1 Hypothyroidism can follow hyperthyroidism.1 Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.1 If an immune-mediated thyroid disorder occurs, withhold or permanently discontinue tislelizumab-jsgr depending on severity.1
Immune-mediated thyroiditis occurred in 1% (25/2390) of patients receiving tislelizumab-jsgr, including grade 2 (0.5%) adverse reactions.1 Thyroiditis did not lead to permanent discontinuation of therapy, but required interruption of therapy in 5 patients.1 Thyroiditis resolved in 36% of patients who developed this adverse reaction, and 2 patients required treatment with systemic corticosteroids.1 All 5 patients in whom tislelizumab-jsgr was withheld for thyroiditis reinitiated tislelizumab-jsgr after symptom improvement and one patient experienced a recurrence.1
Immune-mediated hyperthyroidism occurred in 4.9% (118/2390) of patients receiving tislelizumab-jsgr, including grade 3 (0.04%), and grade 2 (0.9%) adverse reactions.1 Hyperthyroidism led to permanent discontinuation of tislelizumab-jsgr in 1 patient (0.04%) and withholding of tislelizumab-jsgr in 7 patients (0.3%).1 Hyperthyroidism resolved in 76.3% of patients who developed this adverse reaction, and 3 patients received systemic corticosteroids.1 Of the 7 patients in whom tislelizumab-jsgr was withheld for hyperthyroidism, 5 (71.4%) reinitiated tislelizumab-jsgr after symptom improvement and none of these patients had a recurrence.1
Immune-mediated hypothyroidism occurred in 12.5% (299/2390) of patients receiving tislelizumab-jsgr, including grade 4 (0.04%), grade 3 (0.04%), and grade 2 (6.7%) adverse reactions.1 Tislelizumab-jsgr was permanently discontinued in 2 patients, while treatment was withheld in 12 patients (0.5%).1 Among the patients who experienced immune-mediated hypothyroidism, 0.7% received systemic corticosteroids and 65.2% received hormone replacement therapy.1 Hypothyroidism resolved in 34.4% of patients.1 The majority (83.6%) of patients with hypothyroidism required long-term thyroid hormone replacement therapy.1 Of the 12 patients in whom tislelizumab-jsgr was withheld for hypothyroidism, 11 reinitiated tislelizumab-jsgr after symptom improvement and 2 patients experienced a recurrence.1
Type 1 diabetes mellitus has been reported in patients receiving PD-1/PD-L1 blocking antibodies.1 Monitor patients for hyperglycemia or other signs and symptoms of diabetes.1 Initiate treatment with insulin as clinically indicated.1 Withhold or permanently discontinue tislelizumab-jsgr depending on severity.1 Diabetes mellitus occurred in 0.7% (16/2390) of patients receiving tislelizumab-jsgr, including grade 4 (0.1%), grade 3 (0.3%) , and grade 2 (0.3%) adverse reactions.1 Tislelizumab-jsgr was permanently discontinued in 4 patients (0.2%) and required treatment interruption in 4 patients (0.2%).1 Diabetes mellitus resolved in 12.5% of patients who developed this adverse effect; 87.5% received insulin therapy.1 Of the 4 patients in whom tislelizumab-jsgr was withheld for diabetes mellitus, 1 patient reinitiated tislelizumab-jsgr after symptom improvement.1
Tislelizumab-jsgr can cause immune-mediated nephritis, which can be fatal.1
Immune-mediated nephritis with renal dysfunction occurred in 0.2% (5/2390) of patients receiving tislelizumab-jsgr, including grade 3 (0.04%), and grade 2 (0.1%) adverse reactions.1 Tislelizumab-jsgr was permanently discontinued in 1 patient and required interruption of therapy in 3 patients.1 Among the patients who experienced this adverse reaction, 60% received high-dose systemic corticosteroids.1 Nephritis resolved in 40% of patients.1 Of the 3 patients in whom tislelizumab-jsgr was withheld for nephritis, 2 reinitiated therapy after symptom improvement and no patient experienced a recurrence.1
Tislelizumab-jsgr can cause immune-mediated rash or dermatitis.1 Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome.1 Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.1 Withhold or permanently discontinue tislelizumab-jsgr depending on severity.1
Immune-mediated dermatologic adverse reactions occurred in 13% (311/2390) of patients receiving tislelizumab-jsgr, including grade 4 (0.1%), grade 3 (1.1%), and grade 2 (3.4%) adverse reactions.1 One patient experienced SJS.1 Dermatologic adverse reactions led to permanent discontinuation of tislelizumab-jsgr in 3 patients and treatment interruption in 30 patients.1 Among the patients who developed this adverse reaction, 14.1% received systemic corticosteroids and 6.1% received high-dose systemic corticosteroids.1 Immune-mediated dermatologic adverse reactions resolved in 66.9% of patients.1 Of the 30 patients in whom tislelizumab-jsgr was withheld for dermatologic adverse reactions, 26 reinitiated the drug after symptom improvement, and 3 patients experienced a recurrence.1
Other clinically important immune-mediated adverse reactions have been observed rarely with tislelizumab-jsgr (or other anti-PD-1/PD-L1 monoclonal antibodies); in some instances, these reactions were severe or fatal.1
Some cases of ocular adverse reactions may be associated with retinal detachment.1 Various grades of visual impairment (including blindness) can occur.1 If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.1
Tislelizumab-jsgr can cause severe or life-threatening infusion-related reactions.1 Infusion-related reactions occurred in 5% of patients receiving tislelizumab-jsgr, including grade 3 or higher (0.2%) reactions.1
Monitor patients for signs and symptoms of infusion-related reactions.1 Slow the rate of infusion for mild (grade 1) and interrupt the infusion for moderate (grade 2) infusion-related reactions.1 For severe (grade 3) or life-threatening (grade 4) infusion-related reactions, stop the infusion and permanently discontinue therapy.1
Complications of Allogeneic Hematopoietic Stem Cell Transplantation
Serious, and sometimes fatal, complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.1 Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).1 These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.1
Closely monitor patients for evidence of transplant-related complications and intervene promptly.1 Weigh the benefits versus risks of tislelizumab-jsgr therapy prior to or after an allogeneic HSCT.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, tislelizumab-jsgr can cause fetal harm when administered to a pregnant woman.1 Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death.1 Avoid pregnancy during therapy.1 Confirm pregnancy status prior to initiation of therapy in females of reproductive potential.1 Advise females of reproductive potential to use effective contraception during treatment with tislelizumab-jsgr and for 4 months after the last dose.1
In the RATIONALE-302 study in patients with esophageal cancer, the incidence of anti-tislelizumab antibodies among patients who received tislelizumab-jsgr for up to 22 months was 14.5% (32/221).1 Among the anti-tislelizumab antibody-positive patients, the incidence of neutralizing antibodies was 3.1%.1
In patients who received tislelizumab-jsgr for up to 26 months in the RATIONALE-306 study, the incidence of anti-tislelizumab antibodies was 22% (66/300).1 Among the anti-tislelizumab antibody-positive patients, the incidence of neutralizing antibodies was 1.5%.1
In patients who received tislelizumab-jsgr in the RATIONALE-305 study in patients with gastric cancer, the incidence of anti-tislelizumab antibodies was 22.7% (108/475).1 Among the anti-tislelizumab antibody-positive patients, the incidence of neutralizing antibodies was 5.6%.1
Based on its mechanism of action, tislelizumab-jsgr can cause fetal harm when administered during pregnancy.1 There are no available data on the use of tislelizumab-jsgr in pregnant women.1 Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death.1 Human IgG4 immunoglobulins are known to cross the placental barrier; therefore, tislelizumab-jsgr has the potential to be transmitted from the mother to the developing fetus.1 Advise women of the potential risk to a fetus.1
There is no information regarding the presence of tislelizumab-jsgr in human milk, its effects on the breastfed child, or on milk production.1 Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose of the drug.1
Females and Males of Reproductive Potential
Tislelizumab-jsgr can cause fetal harm when administered to a pregnant woman.1 Verify pregnancy status in females of reproductive potential prior to initiating therapy.1
Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of the drug.1
Safety and effectiveness of tislelizumab-jsgr have not been established in pediatric patients.1
Of the 255 patients with esophageal squamous cell carcinoma (ESCC) who were treated with tislelizumab-jsgr in the RATIONALE-302 study, 38% were 65 years of age and older and 5% were 75 years of age and older.1 No overall differences in safety or effectiveness were observed between these geriatric patients and younger patients.1
Of the 324 patients who were treated with tislelizumab-jsgr in combination with platinum-containing chemotherapy as first-line treatment for unresectable advanced or metastatic ESCC in the RATIONALE-306 study, 46% were 65 years of age and older and 4% were 75 years of age and older.1 No overall differences in safety or effectiveness were observed between these geriatric patients and younger patients.1
Of the 498 patients who were treated with tislelizumab-jsgr in combination with platinum-containing chemotherapy for gastric or gastroesophageal junction adenocarcinoma in the RATIONALE-305 study, 32% were 65 years of age and older and 6% were 75 years of age and older.1 No overall differences in safety or effectiveness were observed between these geriatric patients and younger patients.1
No clinically significant differences in the pharmacokinetics of tislelizumab-jsgr were observed based on mild to moderate hepatic impairment (total bilirubin ≤3 times ULN and any AST).1, 2 The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on the pharmacokinetics of tislelizumab is unknown.2
No clinically significant differences in the pharmacokinetics of tislelizumab-jsgr were observed based on mild to moderate renal impairment (estimated creatinine clearance ≥30 mL/minute).1, 2
The most common adverse reactions (≥20%) reported with tislelizumab-jsgr in combination with platinum-containing chemotherapy were decreased neutrophil count, decreased sodium, increased glucose, anemia, fatigue, decreased appetite, increased aspartate aminotransferase (AST), decreased potassium, increased serum creatinine, decreased calcium, increased alanine aminotransferase (ALT), diarrhea, stomatitis, and vomiting.1
The most common adverse reactions (≥20%) reported with tislelizumab-jsgr as a single agent were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.1
The most common (≥20%) adverse reactions reported with tislelizumab-jsgr in combination with platinum and fluropyrimidine-based chemotherapy were nausea, fatigue, decreased appetite, anemia, peripheral sensory neuropathy, vomiting, decreased platelet count, decreased neutrophil count, increased AST, diarrhea, abdominal pain, increased ALT, decreased white blood cell count, decreased weight, and pyrexia.1
Tislelizumab-jsgr is a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody.1 Binding of the programmed death receptor-1 (PD-1) ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production.1 Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.1
Tislelizumab-jsgr binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.1, 2 Tislelizumab-jsgr decreased tumor growth in xenograft models and a human PD-1 transgenic mouse model.1
Steady state concentration of tislelizumab-jsgr is reached after 12 weeks of repeated dosing with an every 3-week regimen with a systemic accumulation of approximately 2-fold.1, 2 Peak plasma concentrations are observed immediately after the end of the infusion.2 The half-life of tislelizumab-jsgr is 24 days.1, 2 No substantial change in pharmacokinetics of tislelizumab-jsgr have been observed based on age, weight, race, or presence of mild to moderate renal or hepatic impairment.1, 2 The effect of severe hepatic impairment, severe renal impairment, or end stage renal disease on the pharmacokinetics of tislelizumab-jsgr is unknown.2
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Tislelizumab-jsgr is obtained through designated specialty pharmacies.3 Contact manufacturer or consult the website ([Web]) for specific availability information.3
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV use | 10 mg/mL | Tevimbra® | BeOne Medicines USA, Inc. |
Only references cited for selected revisions after 1984 are available electronically.
1. BeOne Medicines USA, Inc. TEVIMBRA®(tislelizumab) INTRAVENOUS prescribing information. Pennington, NJ; 2025 Jun.
2. Center for Drug Evaluation and Research. Multi-Discipline Review. Application Number:761232Orig1s000.
3. BeOne Medicines USA, Inc.. How to access and order Brukinsa®(zanubrutinib) and Tevimbra® (tislelizumab-jsgr). From BeOne website. Accessed 2025 Sept 30.
4. Shen L, Kato K, Kim SB et al. Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): a randomized phase III study. J Clin Oncol 2022;40(26):3065-76.
7. Qui MZ, Oh DY, Kato K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ 2024;385:e078876.
8. Xu J, Kato K, Raymond E, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24(5):483-495.
10001. National Cancer Institute. Nasopharyngeal carcinoma treatment (PDQ®) - Health Professional Version. Updated July 25, 2024. [Web]
10002. Yang Y, Pan J, Wang H, et al. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: a multicenter phase 3 trial (RATIONALE-309). Cancer Cell. 2023;41(6):1061-72.e4.