BRIEF SUMMARY

TORIPALIMAB-tpzi-(Oct 2023)

Indn-      to treat recurrent or metastatic nasophygeal carcinoma when or                                 together with or following other therapies

Comp-    Injection: 240 mg/6 mL (40 mg/mL) solution in a single-dose vial    As a single agent:   • 3 mg/kg intravenously every two weeks

 First Infusion: Infuse over 60 minutes.

ADR-   The most common adverse reactions (= 20%) are nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.

CI-  None

WARNINGS -

 • Immune-Mediated Adverse Reactions                                                                             o Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immunemediated hepatitis, immune-mediated endocrinopathies, immune  mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection.

Pt Inform-                                                                                                                Immune-Mediated Adverse Reactions-                                                                            Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of LOQTORZI.

These reactions may include:                                                                                               • Pneumonitis: Advise patients to contact their heal

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U.S.  APPROVED DURING 2023                                        

Serial No 46

Name-          LOQTORZI

Indication              to treat recurrent or metastatic nasophygeal carcinoma when or                                 together with or following other therapies

Date  of approval       10/27/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                               LOQTORZI safely and effectively.

See full prescribing information for LOQTORZI. LOQTORZI (toripalimab-tpzi) injection, for intravenous use

Initial U.S. Approval: 2023

INDICATIONS AND USAGE-

 LOQTORZI is a programmed death receptor-1 (PD-1)- blocking antibody indicated:

• in combination with cisplatin and gemcitabine, for first-line treatment of adults with metastatic or with recurrent locally advanced nasopharyngeal carcinoma (NPC).

 • as a single agent for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy

ADVERSE REACTIONS-

 • LOQTORZI in Combination with Cisplatin and Gemcitabine The most common adverse reactions (= 20%) are nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.

CONTRAINDICATIONS-

 None

WARNINGS AND PRECAUTIONS-

 • Immune-Mediated Adverse Reactions                                                                             o Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immunemediated hepatitis, immune-mediated endocrinopathies, immune  mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection.

o Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.

 o Withhold or permanently discontinue based on severity and type of reaction.

 • Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue LOQTORZI based on the severity of reaction.

 • Complications of allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.

 • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective method of contraception.

DOSAGE AND ADMINISTRATION-

 In combination with cisplatin and gemcitabine: • 240 mg intravenously every three weeks

 As a single agent:                                                                                                                • 3 mg/kg intravenously every two weeks

 First Infusion: Infuse over 60 minutes.

Subsequent Infusions: If no infusion-related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes.

DOSAGE FORMS AND STRENGTHS-

 Injection: 240 mg/6 mL (40 mg/mL) solution in a single-dose vial 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Immune-Mediated Adverse Reactions-                                                                            Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of LOQTORZI.

These reactions may include:                                                                                               • Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath

 • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain

• Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, or easy bruising or bleeding

 • Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, or Type 1 diabetes mellitus

 • Nephritis: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis

 • Severe skin reactions: Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS or TEN

 • Other immune-mediated adverse reactions:                                                             

 o Advise patients that other immune-mediated adverse reactions can occur and may involve any organ system. Advise patients to contact their healthcare provider immediately for any new or worsening signs or symptoms

 o Advise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection

 Infusion-Related Reactions -                                                                                      Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions

 Complications of Allogeneic HSCT-                                                                               Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications

 Embryo-Fetal Toxicity                                                                                                       • Advise females of reproductive potential that LOQTORZI can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy

 • Advise females of reproductive potential to use effective contraception during treatment with LOQTORZI and for 4 months after the last dose

 Use in Specific Populations

 Lactation-                                                                                                                  Advise women not to breastfeed during treatment with LOQTORZI and for 4 months after the last dose

 Laboratory Tests-                                                                                                             Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests

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Manufactured and Distributed by: Coherus BioSciences, Inc. 333 Twin Dolphin Drive, Suite 600 Redwood City, CA 94065, USA U.S. License No. 2023

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                               Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. 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.

2. Pharmacodynamics-                                                                                                       The toripalimab-tpzi exposure-response relationships and time course of pharmacodynamic response are not fully characterized.

3. Pharmacokinetics-                                                                                                   Toripalimab-tpzi pharmacokinetic parameters are presented as geometric mean (coefficient of variation [CV]%) unless otherwise noted.

Toripalimab-tpzi concentrations increased in nonlinearly over the dose range of 0.3 to 10 mg/kg every two weeks (0.1 to 3.3 times the approved recommended 3 mg/kg dosage in a 64 kg patient).

Distribution-                                                                                                                      The mean volume of distribution at steady state (Vss) of toripalimab-tpzi was 3.7 L (27%). 

Elimination-                                                                                                                    The mean clearance (CL) was 14.9 mL/h (31%) after the first dose and 9.5 mL/h (36%) at steady state. The mean terminal half-life (t1/2) (± standard deviation) was 10 ± 1.5 days after the first dose and 18 ± 9.4 days at steady state.

Metabolism-                                                                                                      Toripalimab-tpzi is expected to be metabolized into small peptides by catabolic pathways.

Specific Populations-                                                                                                     No clinically significant differences in the pharmacokinetics were observed based on age (21 to 85 years), body weight (32 to 164 kg), sex, race (White and Asian), concomitant chemotherapy, mild renal impairment (creatinine clearance [CLcr] 60 to 89 mL/min), mild hepatic impairment (total bilirubin > 1 to 1.5 times ULN with any AST or total bilirubin = ULN with AST > ULN), tumor burden and primary cancer.

 Immunogenicity-                                                                                                                 The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                   Based on its mechanism of action, LOQTORZI can cause fetal harm when administered to a pregnant woman [

There are no available data on the use of LOQTORZI in pregnant women.

LOQTORZI can potentially be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

2. Lactation Risk Summary-                                                                                          There are no data on the presence of toripalimab-tpzi in human milk or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk.

The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to toripalimab-tpzi are unknown.

Because of the potential for serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment with LOQTORZI and for 4 months after the last dose.

3. Females and Males of Reproductive Potential-                                                           LOQTORZI can cause fetal harm when administered to a pregnant woman .

Pregnancy Testing -                                                                                                     Verify the pregnancy status of females of reproductive potential prior to initiating LOQTORZI [see Use in Specific Populations (8.1)].

Contraception Females -                                                                                                 Advise females of reproductive potential to use effective contraception during treatment with LOQTORZI and for 4 months after the last dose.

4. Pediatric Use The safety and effectiveness of LOQTORZI have not been established in pediatric patients [see Indications and Usage (1)].

5. Geriatric Use Of the 146 patients with NPC who were treated with LOQTORZI in combination with cisplatin and gemcitabine 7 (4.8%) were 65 years or older; there were no patients 75 years and older.