- Approval Id
- 6e198062b7f3f5d7
- Drug Approval Emc Name
- LOQTORZI 240 mg/6 ml Concentrate for Solution for Infusion
- Drug Name
- LOQTORZI 240 mg/6 ml Concentrate for Solution for Infusion
- Company Address
- Suite 205, The Greenway, Ardilaun Court Block C, 112-114 Saint Stephen's Green, Dublin, D02 TD28, Ireland
- Company Website
- www.topalliancebio.com
- Company Telephone
- +44 7917790417
- Company Medical Info Direct Line
- +44 (0)1844 347333
- Company Medical Info Email
- [email protected]
- Atc Code
- L01FF13
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Topalliance Biosciences Europe Limited Ground Floor Two Dockland Central Guild Street I.f.s.c. Dublin 1 Co. Dublin D01 K2C5 Ireland
- Authorisation Number
- 8. Marketing authorisation number(s) PL 60874/0001
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 15 November 2024
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Topalliance Biosciences Europe Limited Ground Floor Two Dockland Central Guild Street I.f.s.c. Dublin 1 Co. Dublin D01 K2C5 Ireland
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 60874/0001
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 15 November 2024
- Instruction Composition
- 2. Qualitative and quantitative composition One vial of concentrate for solution for infusion contains 240 mg of toripalimab. Each mL of concentrate for solution for infusion contains 40 mg of toripalimab. Toripalimab is an immunoglobulin G4 (IgG4) humanised monoclonal antibody (mAb), produced in Chinese hamster ovary cells by recombinant DNA technology. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Concentrate for solution for infusion. Clear to slightly opalescent, colourless to slightly yellow solution essentially free from visible particles. The concentrate for solution has a pH of 5.5 – 6.5 and an osmolality of 260‑340 mOsmol/kg.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications LOQTORZI, in combination with cisplatin and gemcitabine, is indicated for the first‑line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma. LOQTORZI, in combination with cisplatin and paclitaxel, is indicated for the first‑line treatment of adult patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. 4.2 Posology and method of administration Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Posology The recommended dosing regimen of LOQTORZI is 240 mg every 3 weeks (Q3W) as an intravenous infusion over 60 minutes for the first infusion. If no significant infusion‑related reactions occurred during the first infusion, the subsequent infusions may be administered over 30 minutes. Treatment should continue until disease progression, unacceptable toxicity or up to a maximum duration of 24 months. Dose modifications Recommended modifications to manage adverse reaction are provided in Table 1. See the Summary of Product Characteristics (SmPC) of other products to be used in combination with LOQTORZI. Table 1: Recommended treatment modifications for LOQTORZI Adverse reaction Severity1 Treatment modification Immune‑related adverse reactions Pneumonitis Grade 2 Withhold2 Grades 3 or 4 Permanently discontinue Diarrhoea/colitis Grade 2 or 3 Withhold2 Grade 4 Permanently discontinue Hepatitis Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) increases to more than 3 and up to 5 times the upper limit of normal (ULN) or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold2 AST or ALT increases to more than 5 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grade 2‑4 adrenal insufficiency or hypophysitis Withhold until clinically stable on hormone replacement therapy2 Grades 3 or 4 hyperthyroidism or thyroiditis Withhold until clinically stable on appropriate medical management Grade 3‑4 diabetes mellitus Withhold until clinically stable on antihyperglycemic (insulin) therapy Grade 1‑4 hypothyroidism Manage with hormone replacement therapy without toripalimab interruption Nephritis with renal dysfunction Grade 2‑3 increased blood creatinine Withhold2 Grade 4 increased blood creatinine Permanently discontinue Exfoliative dermatologic conditions Suspected Stevens‑Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) Withhold2 Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grades 2, 3, or 4 Permanently discontinue Myositis Grade 2‑3 Withhold or permanently discontinue depending on severity2 Grade 4 Permanently discontinue Other adverse reactions (including but not limited to neurologic toxicities, pancreatitis, iritis, uveitis, immune‑related cystitis, and immune‑related inflammatory arthritis) Grade 2‑3 Withhold or permanently discontinue depending on type and severity2 Grade 4 Permanently discontinue Infusion‑related reactions Infusion‑related reactions Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Stop infusion. Permanently discontinue 1 Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antineoplastic agents, ATC code: L01FF13 Mechanism of action Toripalimab is a humanised IgG4 monoclonal antibody that binds to the PD‑1 receptor and blocks its interaction with PD‑L1 and PD‑L2, releasing PD‑1 pathway‑mediated inhibition of the immune response, including the anti‑tumour immune response. Binding of the PD‑1 ligands, PD‑L1 and PD‑L2, to the PD‑1 receptor found on T cells, inhibits T cell proliferation, cytokine production, and cytotoxic activity. Clinical efficacy and safety Nasopharyngeal carcinoma The efficacy of toripalimab in combination with cisplatin and gemcitabine was investigated in JUPITER‑02, a randomised, multi‑centre, double‑blind, placebo‑controlled study in 289 patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC) not amenable to curative therapy who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients with recurrent NPC after treatment with curative intent were required to have an interval of at least 6 months between the last dose of radiotherapy or chemotherapy and recurrence. Patients with autoimmune disease, other than stable hypothyroidism or Type I diabetes, and patients who required systemic immunosuppression were ineligible. Randomisation was stratified according to ECOG PS (0 versus 1) and disease stage (recurrent versus metastatic) at study entry. Patients were randomised (1:1) to receive one of the following treatments: • Toripalimab 240 mg intravenously on Day 1 in combination with cisplatin 80 mg/m2 on Day 1 and gemcitabine 1 000 mg/m2 on Days 1 and 8 every 3 weeks for up to 6 cycles, followed by toripalimab 240 mg once every 3 weeks, or • Placebo intravenously on Day 1 in combination with cisplatin 80 mg/m2 on Day 1 and gemcitabine 1 000 mg/m2 on Days 1 and 8 every 3 weeks for up to 6 cycles, followed by placebo once every 3 weeks. Treatment with toripalimab or placebo continued until disease progression per response evaluation criteria in solid tumours (RECIST) v1.1 (with the exception noted below), unacceptable toxicity, or a maximum of 2 years. Administration of toripalimab was permitted beyond radiographic progression if the patient was deriving benefit as assessed by the investigator. Tumour assessments were performed every 6 weeks for the first 12 months and every 9 weeks thereafter. The main efficacy outcome measure was Blinded Independent Review Committee (BIRC)‑assessed progression‑free survival (PFS) according to RECIST v1.1. The study population characteristics were: median age of 48 years (range: 19 to 72), 4.8% age 65 or older, 83% male, 100% Asian, and ECOG PS of 0 (57%) or 1 (43%). Approximately 86% of the study population had metastatic disease at randomisation, with histological subtypes of NPC including 98% non‑keratinizing, 1% keratinizing squamous cell carcinoma, and 1% unclassified NPC/other. The majority (63%) of patients had serum Epstein-Barr virus (EBV) titres ≥ 2000 U/mL. The study showed statistically significant improvements in BIRC‑assessed PFS and OS for patients randomised to toripalimab in combination with cisplatin/gemcitabine compared to cisplatin and gemcitabine with placebo. Efficacy results are summarised in Table 3, Figure 1 and Figure 2 below. Table 3: Efficacy results in JUPITER‑02 Endpoints1 Toripalimab + cisplatin/ gemcitabine N =146 Placebo + cisplatin/ gemcitabine N =143 BIRC‑assessed progression‑free survival (PFS) Number of PFS events (%) 63 (43.2) 87 (60.8) Median PFS, months (95% CI) 21.4 (11.7, NE) 8.2 (7.0, 9.8) Hazard ratio (95% CI)2 0.52 (0.37, 0.73) Nominal p‑value3 < 0.0001 Overall survival (OS) Number of deaths (%) 57 (39.0) 76 (53.1) Median OS, in months (95% CI) NE (38.7, NE) 33.7 (27.0, 44.2) Hazard ratio (95% CI)2 0.63 (0.45, 0.89) p‑value3 0.0083 1 The final analysis of PFS was based on the data with cut‑off date of 08 Jun 2021 and the final analysis of OS was based on the data with cut‑off date of 18 Nov 2022. 2The hazard ratio and its confidence interval were computed using a stratified Cox proportional‑hazards model. 3Two‑sided p‑value, based on stratified log‑rank test. BIRC=blinded independent review committee; CI= confidence interval; NE=Not estimable Figure 1: Kaplan‑Meier curves for BIRC‑assessed PFS in JUPITER‑02 data cut‑off date: 08 Jun 2021 Figure 2: Kaplan‑Meier curves for overall survival in JUPITER‑02 data cut‑off date: 18 Nov 2022 In exploratory subgroup analyses of PFS and OS, the magnitude of the treatment effects appeared similar across patient subgroups based on PD‑L1 expression or EBV titres. Elderly population A minority of patients (4.8%; 14/289) were age ≥ 65 years. Data are too limited to draw conclusions on this population. Oesophageal squamous cell carcinoma The efficacy of toripalimab in combination with paclitaxel and cisplatin was investigated in JUPITER‑06, a randomised, multi‑centre, single region, double‑blind, placebo‑controlled study in 514 patients with metastatic or recurrent, locally advanced oesophageal squamous cell carcinoma (OSCC) who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients with recurrent OSCC after treatment with curative intent were required to have an interval of at least 6 months between the last dose of adjuvant, neoadjuvant chemotherapy, radiation, or chemoradiotherapy and recurrence or at least 12 months between the last dose of adjuvant chemotherapy/chemoradiotherapy with paclitaxel and cisplatin. Patients with autoimmune disease, other than stable hypothyroidism or Type I diabetes, and patients who required systemic immunosuppression were ineligible. Randomisation was stratified according to ECOG PS (0 versus 1) and previous radiotherapy (yes versus no). Patients were randomized (1:1) to receive one of the following treatments: • Toripalimab 240 mg intravenously in combination with paclitaxel 175 mg/m2 intravenously and cisplatin 75 mg/m2intravenously on Day 1 every 3 weeks for 4 to 6 cycles, followed by toripalimab 240 mg once every 3 weeks, or • Placebo intravenously in combination with paclitaxel 175 mg/ m2 intravenously and cisplatin 75 mg/m2 intravenously on Day 1 every 3 weeks for 4 to 6 cycles, followed by placebo once every 3 weeks. Treatment with toripalimab or placebo continued until disease progression per RECIST v1.1, unacceptable toxicity (with the exception noted below), or a maximum of 2 years. Tumour assessments were performed every 6 weeks for the first 12 months and every 9 weeks thereafter. The co‑primary endpoints were Blinded Independent Review Committee (BIRC)‑assessed progression‑free survival (PFS) according to RECIST v1.1 and OS. The study population characteristics were: median age of 63 years (range: 20 to 75), 38% age 65 or older, 85% male, 100% Asian, and ECOG PS of 0 (26%) or 1 (74%). Seventy‑nine percent of patients had metastatic disease at study entry. The results of the final analysis of BIRC‑determined PFS showed a statistically significant improvement in PFS. At the final analysis of OS (data cut‑off 23 Feb 2023), the study showed consistent improvement in OS (HR 0.72; 95% CI 0.58‑0.88). Efficacy results of OS and BIRC‑determined PFS are summarised in Table 4, Figure 3 and Figure 4 below. Table 4: Efficacy results in JUPITER‑06 Toripalimab + paclitaxel/cisplatin N = 257 Placebo + paclitaxel/cisplatin N = 257 Overall survival (OS)1 Number of OS events (%) 172 (6
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Citric acid monohydrate Mannitol Polysorbate 80 Sodium chloride Sodium citrate dihydrate Water for injections 6.2 Incompatibilities This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. 6.3 Shelf life Unopened vial 3 years. After dilution Chemical and physical in‑use stability after dilution has been demonstrated for 24 hours at 2°C to 8°C or at 20°C to 25°C. From a microbiological point of view, unless the method of dilution precludes the risks of microbial contamination, the product should be used immediately. If not used immediately, in‑use storage times and conditions are the responsibility of the user. 6.4 Special precautions for storage Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original carton in order to protect from light. For storage conditions after dilution of the medicinal product, see section 6.3. 6.5 Nature and contents of container Type 1 neutral borosilicate glass vial capped sealed with a chlorobutyl rubber stopper and sealed with a 20 mm flip‑off seal (aluminium), containing 6 mL of concentrate for solution for infusion. Each carton contains one vial. 6.6 Special precautions for disposal and other handling Preparation • Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colourless to slightly yellow. Discard the vial if visible particles are observed. • Dilute LOQTORZI prior to intravenous administration. • Withdraw the required volume of LOQTORZI and inject slowly into a 100 mL or 250 mL infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection. Mix the diluted solution by gentle inversion. Do not shake. The final concentration of the diluted solution should be between 1 mg/mL to 3 mg/mL. Administration • Administer the diluted solution intravenously via an infusion pump using a sterile in-line filter (0.2 micron or 0.22 micron pore size). • First infusion: infuse over at least 60 minutes. • Subsequent infusions: if no infusion‑related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes. • Do not co‑administer other medicinal products through the same intravenous line. • When administered on the same day as chemotherapy, LOQTORZI should be administered prior to chemotherapy. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition One vial of concentrate for solution for infusion contains 240 mg of toripalimab. Each mL of concentrate for solution for infusion contains 40 mg of toripalimab. Toripalimab is an immunoglobulin G4 (IgG4) humanised monoclonal antibody (mAb), produced in Chinese hamster ovary cells by recombinant DNA technology. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Concentrate for solution for infusion. Clear to slightly opalescent, colourless to slightly yellow solution essentially free from visible particles. The concentrate for solution has a pH of 5.5 – 6.5 and an osmolality of 260‑340 mOsmol/kg.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications LOQTORZI, in combination with cisplatin and gemcitabine, is indicated for the first‑line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma. LOQTORZI, in combination with cisplatin and paclitaxel, is indicated for the first‑line treatment of adult patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. 4.2 Posology and method of administration Treatment must be initiated and supervised by physicians experienced in the treatment of cancer. Posology The recommended dosing regimen of LOQTORZI is 240 mg every 3 weeks (Q3W) as an intravenous infusion over 60 minutes for the first infusion. If no significant infusion‑related reactions occurred during the first infusion, the subsequent infusions may be administered over 30 minutes. Treatment should continue until disease progression, unacceptable toxicity or up to a maximum duration of 24 months. Dose modifications Recommended modifications to manage adverse reaction are provided in Table 1. See the Summary of Product Characteristics (SmPC) of other products to be used in combination with LOQTORZI. Table 1: Recommended treatment modifications for LOQTORZI Adverse reaction Severity1 Treatment modification Immune‑related adverse reactions Pneumonitis Grade 2 Withhold2 Grades 3 or 4 Permanently discontinue Diarrhoea/colitis Grade 2 or 3 Withhold2 Grade 4 Permanently discontinue Hepatitis Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) increases to more than 3 and up to 5 times the upper limit of normal (ULN) or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold2 AST or ALT increases to more than 5 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grade 2‑4 adrenal insufficiency or hypophysitis Withhold until clinically stable on hormone replacement therapy2 Grades 3 or 4 hyperthyroidism or thyroiditis Withhold until clinically stable on appropriate medical management Grade 3‑4 diabetes mellitus Withhold until clinically stable on antihyperglycemic (insulin) therapy Grade 1‑4 hypothyroidism Manage with hormone replacement therapy without toripalimab interruption Nephritis with renal dysfunction Grade 2‑3 increased blood creatinine Withhold2 Grade 4 increased blood creatinine Permanently discontinue Exfoliative dermatologic conditions Suspected Stevens‑Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) Withhold2 Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis Grades 2, 3, or 4 Permanently discontinue Myositis Grade 2‑3 Withhold or permanently discontinue depending on severity2 Grade 4 Permanently discontinue Other adverse reactions (including but not limited to neurologic toxicities, pancreatitis, iritis, uveitis, immune‑related cystitis, and immune‑related inflammatory arthritis) Grade 2‑3 Withhold or permanently discontinue depending on type and severity2 Grade 4 Permanently discontinue Infusion‑related reactions Infusion‑related reactions Grade 1 or 2 Interrupt or slow the rate of infusion Grade 3 or 4 Stop infusion. Permanently discontinue 1 Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antineoplastic agents, ATC code: L01FF13 Mechanism of action Toripalimab is a humanised IgG4 monoclonal antibody that binds to the PD‑1 receptor and blocks its interaction with PD‑L1 and PD‑L2, releasing PD‑1 pathway‑mediated inhibition of the immune response, including the anti‑tumour immune response. Binding of the PD‑1 ligands, PD‑L1 and PD‑L2, to the PD‑1 receptor found on T cells, inhibits T cell proliferation, cytokine production, and cytotoxic activity. Clinical efficacy and safety Nasopharyngeal carcinoma The efficacy of toripalimab in combination with cisplatin and gemcitabine was investigated in JUPITER‑02, a randomised, multi‑centre, double‑blind, placebo‑controlled study in 289 patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC) not amenable to curative therapy who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients with recurrent NPC after treatment with curative intent were required to have an interval of at least 6 months between the last dose of radiotherapy or chemotherapy and recurrence. Patients with autoimmune disease, other than stable hypothyroidism or Type I diabetes, and patients who required systemic immunosuppression were ineligible. Randomisation was stratified according to ECOG PS (0 versus 1) and disease stage (recurrent versus metastatic) at study entry. Patients were randomised (1:1) to receive one of the following treatments: • Toripalimab 240 mg intravenously on Day 1 in combination with cisplatin 80 mg/m2 on Day 1 and gemcitabine 1 000 mg/m2 on Days 1 and 8 every 3 weeks for up to 6 cycles, followed by toripalimab 240 mg once every 3 weeks, or • Placebo intravenously on Day 1 in combination with cisplatin 80 mg/m2 on Day 1 and gemcitabine 1 000 mg/m2 on Days 1 and 8 every 3 weeks for up to 6 cycles, followed by placebo once every 3 weeks. Treatment with toripalimab or placebo continued until disease progression per response evaluation criteria in solid tumours (RECIST) v1.1 (with the exception noted below), unacceptable toxicity, or a maximum of 2 years. Administration of toripalimab was permitted beyond radiographic progression if the patient was deriving benefit as assessed by the investigator. Tumour assessments were performed every 6 weeks for the first 12 months and every 9 weeks thereafter. The main efficacy outcome measure was Blinded Independent Review Committee (BIRC)‑assessed progression‑free survival (PFS) according to RECIST v1.1. The study population characteristics were: median age of 48 years (range: 19 to 72), 4.8% age 65 or older, 83% male, 100% Asian, and ECOG PS of 0 (57%) or 1 (43%). Approximately 86% of the study population had metastatic disease at randomisation, with histological subtypes of NPC including 98% non‑keratinizing, 1% keratinizing squamous cell carcinoma, and 1% unclassified NPC/other. The majority (63%) of patients had serum Epstein-Barr virus (EBV) titres ≥ 2000 U/mL. The study showed statistically significant improvements in BIRC‑assessed PFS and OS for patients randomised to toripalimab in combination with cisplatin/gemcitabine compared to cisplatin and gemcitabine with placebo. Efficacy results are summarised in Table 3, Figure 1 and Figure 2 below. Table 3: Efficacy results in JUPITER‑02 Endpoints1 Toripalimab + cisplatin/ gemcitabine N =146 Placebo + cisplatin/ gemcitabine N =143 BIRC‑assessed progression‑free survival (PFS) Number of PFS events (%) 63 (43.2) 87 (60.8) Median PFS, months (95% CI) 21.4 (11.7, NE) 8.2 (7.0, 9.8) Hazard ratio (95% CI)2 0.52 (0.37, 0.73) Nominal p‑value3 < 0.0001 Overall survival (OS) Number of deaths (%) 57 (39.0) 76 (53.1) Median OS, in months (95% CI) NE (38.7, NE) 33.7 (27.0, 44.2) Hazard ratio (95% CI)2 0.63 (0.45, 0.89) p‑value3 0.0083 1 The final analysis of PFS was based on the data with cut‑off date of 08 Jun 2021 and the final analysis of OS was based on the data with cut‑off date of 18 Nov 2022. 2The hazard ratio and its confidence interval were computed using a stratified Cox proportional‑hazards model. 3Two‑sided p‑value, based on stratified log‑rank test. BIRC=blinded independent review committee; CI= confidence interval; NE=Not estimable Figure 1: Kaplan‑Meier curves for BIRC‑assessed PFS in JUPITER‑02 data cut‑off date: 08 Jun 2021 Figure 2: Kaplan‑Meier curves for overall survival in JUPITER‑02 data cut‑off date: 18 Nov 2022 In exploratory subgroup analyses of PFS and OS, the magnitude of the treatment effects appeared similar across patient subgroups based on PD‑L1 expression or EBV titres. Elderly population A minority of patients (4.8%; 14/289) were age ≥ 65 years. Data are too limited to draw conclusions on this population. Oesophageal squamous cell carcinoma The efficacy of toripalimab in combination with paclitaxel and cisplatin was investigated in JUPITER‑06, a randomised, multi‑centre, single region, double‑blind, placebo‑controlled study in 514 patients with metastatic or recurrent, locally advanced oesophageal squamous cell carcinoma (OSCC) who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients with recurrent OSCC after treatment with curative intent were required to have an interval of at least 6 months between the last dose of adjuvant, neoadjuvant chemotherapy, radiation, or chemoradiotherapy and recurrence or at least 12 months between the last dose of adjuvant chemotherapy/chemoradiotherapy with paclitaxel and cisplatin. Patients with autoimmune disease, other than stable hypothyroidism or Type I diabetes, and patients who required systemic immunosuppression were ineligible. Randomisation was stratified according to ECOG PS (0 versus 1) and previous radiotherapy (yes versus no). Patients were randomized (1:1) to receive one of the following treatments: • Toripalimab 240 mg intravenously in combination with paclitaxel 175 mg/m2 intravenously and cisplatin 75 mg/m2intravenously on Day 1 every 3 weeks for 4 to 6 cycles, followed by toripalimab 240 mg once every 3 weeks, or • Placebo intravenously in combination with paclitaxel 175 mg/ m2 intravenously and cisplatin 75 mg/m2 intravenously on Day 1 every 3 weeks for 4 to 6 cycles, followed by placebo once every 3 weeks. Treatment with toripalimab or placebo continued until disease progression per RECIST v1.1, unacceptable toxicity (with the exception noted below), or a maximum of 2 years. Tumour assessments were performed every 6 weeks for the first 12 months and every 9 weeks thereafter. The co‑primary endpoints were Blinded Independent Review Committee (BIRC)‑assessed progression‑free survival (PFS) according to RECIST v1.1 and OS. The study population characteristics were: median age of 63 years (range: 20 to 75), 38% age 65 or older, 85% male, 100% Asian, and ECOG PS of 0 (26%) or 1 (74%). Seventy‑nine percent of patients had metastatic disease at study entry. The results of the final analysis of BIRC‑determined PFS showed a statistically significant improvement in PFS. At the final analysis of OS (data cut‑off 23 Feb 2023), the study showed consistent improvement in OS (HR 0.72; 95% CI 0.58‑0.88). Efficacy results of OS and BIRC‑determined PFS are summarised in Table 4, Figure 3 and Figure 4 below. Table 4: Efficacy results in JUPITER‑06 Toripalimab + paclitaxel/cisplatin N = 257 Placebo + paclitaxel/cisplatin N = 257 Overall survival (OS)1 Number of OS events (%) 172 (6
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Citric acid monohydrate Mannitol Polysorbate 80 Sodium chloride Sodium citrate dihydrate Water for injections 6.2 Incompatibilities This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. 6.3 Shelf life Unopened vial 3 years. After dilution Chemical and physical in‑use stability after dilution has been demonstrated for 24 hours at 2°C to 8°C or at 20°C to 25°C. From a microbiological point of view, unless the method of dilution precludes the risks of microbial contamination, the product should be used immediately. If not used immediately, in‑use storage times and conditions are the responsibility of the user. 6.4 Special precautions for storage Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original carton in order to protect from light. For storage conditions after dilution of the medicinal product, see section 6.3. 6.5 Nature and contents of container Type 1 neutral borosilicate glass vial capped sealed with a chlorobutyl rubber stopper and sealed with a 20 mm flip‑off seal (aluminium), containing 6 mL of concentrate for solution for infusion. Each carton contains one vial. 6.6 Special precautions for disposal and other handling Preparation • Visually inspect the solution for particulate matter and discoloration. The solution is clear to slightly opalescent, colourless to slightly yellow. Discard the vial if visible particles are observed. • Dilute LOQTORZI prior to intravenous administration. • Withdraw the required volume of LOQTORZI and inject slowly into a 100 mL or 250 mL infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection. Mix the diluted solution by gentle inversion. Do not shake. The final concentration of the diluted solution should be between 1 mg/mL to 3 mg/mL. Administration • Administer the diluted solution intravenously via an infusion pump using a sterile in-line filter (0.2 micron or 0.22 micron pore size). • First infusion: infuse over at least 60 minutes. • Subsequent infusions: if no infusion‑related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes. • Do not co‑administer other medicinal products through the same intravenous line. • When administered on the same day as chemotherapy, LOQTORZI should be administered prior to chemotherapy. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Company Detail Path
- /organization/topalliance-biosciences-europe-limited
