Penpulimab kcqx

5 WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions ( 5.1 ) 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, immune-mediated hepatitis and hepatotoxicity, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and 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 penpulimab-kcqx based on severity and type of reaction. Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue penpulimab-kcqx based on the severity of the reaction. ( 5.2 ) 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. ( 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions Penpulimab-kcqx is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD- L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue penpulimab-kcqx depending on severity [see Dosage and Administration (2) ] . In general, if penpulimab-kcqx requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month [ see Dosage and A dministration (2) ] . Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis Penpulimab-kcqx can cause immune-mediated pneumonitis. 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. Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Immune-mediated pneumonitis occurred in 0.7% (1/146) of patients receiving penpulimab-kcqx, which was a Grade 2 (0.7%) adverse reaction. Systemic corticosteroids were required in the patient. Pneumonitis led to withholding of penpulimab-kcqx in the patient. Penpulimab-kcqx as a Single Agent Immune-mediated pneumonitis occurred in 1.3% (5/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.5%), Grade 2 (0.5%) and Grade 1 (0.3%) adverse reactions. Systemic corticosteroids were required in 80% (4/5) of patients with pneumonitis. Pneumonitis led to permanent discontinuation of penpulimab-kcqx in 0.8% (3/372). Pneumonitis resolved in 20% (1/5) of these patients. Immune -Mediated Colitis Penpulimab-kcqx can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus (CMV) infection/reactivation can occur in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Penpulimab-kcqx as a Single Agent Immune-mediated colitis occurred in 1.1% (4/372) of patients receiving penpulimab-kcqx, including Grade 2 (0.8%) and Grade 1 (0.3%) adverse reactions. Systemic corticosteroids were required in 75% (3/4) of patients with colitis. Colitis led to withholding of penpulimab-kcqx in 0.8% (3/372) of patients. Immune-Mediated Hepatitis and Hepatotoxicity Penpulimab-kcqx can cause immune-mediated hepatitis. Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Immune-mediated hepatitis occurred in 0.7% (1/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, which was a Grade 2 (0.7%) adverse reaction. Systemic corticosteroids and withholding of penpulimab-kcqx were required in this patient. Penpulimab-kcqx as a Single Agent Immune-mediated hepatitis occurred in 3.8% (14/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.8%), Grade 2 (1.3%) and Grade 1 (1.6%) adverse reactions. Systemic corticosteroids were required in 14% (2/14) of patients with hepatitis. Hepatitis led to permanent discontinuation of penpulimab-kcqx in 0.3% (1/372) and withholding of penpulimab-kcqx in 2.2% (8/372) of patients. Hepatitis resolved in 64% (9/14) of these patients. Immune-Mediated Endocrinopathies Adrenal Insufficiency Penpulimab-kcqx can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold penpulimab-kcqx depending on severity [see Dosage and Administration (2.2) ]. Hypophysitis Penpulimab-kcqx can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue penpulimab-kcqx depending on severity [see Dosage and Administration (2.2) ]. Thyroid Disorders: Penpulimab-kcqx can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue penpulimab-kcqx based on the severity [ see Dosage and Administration (2) ] . Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (3/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (0.7%) and Grade 1 (1.4%) adverse reactions. Hypothyroidism: Immune-mediated hypothyroidism occurred in 16% (26/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (13%) and Grade 1 (4.8%) adverse reactions. Penpulimab-kcqx was withheld in 0.7% (1/146) of patients. Hypothyroidism resolved in 12% (3/26) of these patients. Penpulimab-kcqx as a Single Agent Thyroiditis: Thyroiditis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including Grade 2 (0.3%) and Grade 1 (0.3%) adverse reactions. Thyroiditis led to withholding of penpulimab-kcqx in 0.3% (1/372) of patients. Thyroiditis was resolved in 50% (1/2) of patients. Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 7% (24/372) of patients receiving penpulimab-kcqx, including Grade 2 (1.1%) and Grade 1 (5%) adverse reactions. Penpulimab-kcqx was withheld in 0.5% (2/372) of patients. Hyperthyroidism resolved in 79% (19/24) of these patients. Hypothyroidism: Immune-mediated hypothyroidism occurred in 19% (69/372) of patients receiving penpulimab-kcqx, including Grade 2 (7%) and Grade 1 (12%) adverse reactions. Penpulimab-kcqx was withheld in 1.6% (6/372) of patients. Hypothyroidism resolved in 48% (33/69) of these patients. Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold penpulimab-kcqx depending on severity [ see Dosage and Administration (2) ]. Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Diabetes occurred in 2.7% (4/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 4 (0.7%), Grade 3 (0.7%), Grade 2 (0.7%) and Grade 1 (0.7%) adverse reactions. Diabetes led to permanent discontinuation of penpulimab-kcqx in 0.7% (1/146) and withholding of penpulimab-kcqx in 0.7% (1/146) of patients. Diabetes was resolving in 75% (3/4) of these patients. Penpulimab-kcqx as a Single Agent Diabetes occurred in 0.8% (3/372) of patients receiving penpulimab-kcqx as a single agent, including Grade 1 (0.8%) adverse reactions. Diabetes resolved in 67% (2/3) of these patients. Immune-Mediated Nephritis with Renal Dysfunction Penpulimab-kcqx can cause immune-mediated nephritis and renal dysfunction. Penpulimab-kcqx as a Single Agent Immune-mediated nephritis occurred in 0.5% (2/372) of patients receiving penpulimab-kcqx, including Grade 3 (0.3%) and Grade 2 (0.3%) adverse reactions. Immune-mediated nephritis led to permanent discontinuation of penpulimab-kcqx in 0.5% (2/372) of patients. Systemic corticosteroids were required in 50% (1/2) of patients. Nephritis resolved in 50% (1/2) of these patients. Immune-Mediated Dermatolog ic Adverse Reactions Penpulimab-kcqx can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN) has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue penpulimab-kcqx depending on severity [see Dosage and Administration (2) ] . Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Immune-mediated rash or dermatitis occurred in 10% (14/146) of patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 3 (0.7%), Grade 2 (4.8%) and Grade 1 (4.1%) adverse reactions. Systemic corticosteroids were required in 36% (5/14) of patients with immune-mediated rash or dermatitis. Immune-mediated rash or dermatitis led to withholding of penpulimab-kcqx in 1.4% (2/146) of patients. Immune-mediated rash or dermatitis resolved in 78.6% (11/14) of these patients. Penpulimab-kcqx as a Single Agent Immune-mediated rash or dermatitis occurred in 12% (43/372) of patients receiving penpulimab-kcqx, including Grade 3 (1.3%), Grade 2 (3.5%) and Grade 1 (7%) adverse reactions. Systemic corticosteroids were required in 14% (6/43) of patients with immune-mediated rash or dermatitis. Immune-mediated rash or dermatitis led to permanent discontinuation of penpulimab-kcqx in 0.3% (1/372) and withholding of penpulimab-kcqx in 1.6% (6/372) of patients. Immune-mediated rash or dermatitis resolved in 58% (25/43) of these patients. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine or single-agent penpulimab-kcqx or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, nerve injury. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment including blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and Connective Tissue : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine: Hypoparathyroidism. Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection. Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reported as the co-occurrence of either two or all three adverse reactions. 5.2 Infusion-Related Reactions Penpulimab-kcqx can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis. Discontinue penpulimab-kcqx in patients with severe or life-threatening infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild or moderate infusion-related reactions [see Dosage and Administration (2) ]. Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine Infusion-related reactions occurred in 3.4% of 146 patients receiving penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, including Grade 2 (1.4%) and Grade 1 (2.1%) infusion related reactions. Penpulimab-kcqx as a Single Agent Infusion-related reactions occurred in 10% of 372 patients receiving penpulimab-kcqx as single agent, including Grade 4 (0.3%), Grade 3 (0.3%), Grade 2 (6%) and Grade 1 (3.8%) infusion related reactions. Penpulimab-kcqx was withheld in 0.8% (3/372) and permanently discontinued in 0.3% (1/372) of patients. 5.3 Complications of Allogeneic HSCT Fatal and other serious 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. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause) [see Adverse Reactions (6.1) ]. These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and Allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an Allogeneic HSCT. 5.4 Embryo-Fetal Toxicity Based on its mechanism of action, penpulimab-kcqx can cause fetal harm when administered to a pregnant woman. 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. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with penpulimab-kcqx and for 4 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) ].

6 ADVERSE REACTIONS The following adverse reactions are described in other sections of the labeling: Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Infusion-Related Reactions[see Warnings and Precautions (5.2) ] Complications of Allogeneic HSCT [see Warnings and Precautions (5.3) ] Penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine : The most common adverse reactions (≥20%) were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia. ( 6.1 ) Penpulimab-kcqx as a single agent : The most common adverse reactions (≥20%) were anemia and hypothyroidism. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Akeso Biopharma Co., Ltd. at toll-free phone 833-662-5376 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to those observed in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in the WARNINGS AND PRECAUTIONS reflect exposure to penpulimab-kcqx in 146 patients in Study AK105-304 [see Clinical Studies (14.1) ] . Patients received 6 cycles every 3 weeks of intravenous penpulimab-kcqx 200 mg in combination with either cisplatin 80 mg/m 2 or carboplatin AUC 5 and gemcitabine 1000 mg/m 2 followed by single-agent penpulimab-kcqx 200 mg every 3 weeks until disease progression or a maximum of 24 months. Among the 146 patients who received penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, 71% were exposed for 6 months or longer and 38% were exposed for greater than one year. In this safety population, the most common (≥ 20%) adverse reactions were nausea (58%), vomiting (55%), hypothyroidism (45%), constipation (41%), decreased appetite (36%), decreased weight (26%), cough (25%), COVID-19 infection (25%), fatigue (25%), rash (24%) and pyrexia (21%). The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes (70%), decreased neutrophils (61%), decreased white blood cells (58%), decreased hemoglobin (49%), decreased platelets (33%), decreased potassium (14%), increased lipase (11%), increased ALT (8%), decreased sodium (7%), increased AST (6%), increased triglycerides (4.3%), decreased magnesium (4.2%), decreased CPK (4.1%), increased amylase (2.9%), increased potassium (2.8%), increased cholesterol (2.2%), increased calcium (2.1%) and increased blood bilirubin (2.1%). The data described in the WARNINGS AND PRECAUTIONS also reflect exposure to single-agent intravenous penpulimab-kcqx 200 mg every 2 weeks until disease progression or a maximum of 24 months in 372 patients in studies: AK105-101 [NCT03352531], AK-105-201 [NCT03722147], AK105-202 [see Clinical Studies (14.2)] , AK105-204 [NCT 04172506]. Among the 372 patients who received single-agent penpulimab-kcqx, 49% were exposed for 6 months or longer and 34% were exposed for at least one year. In this safety population, the most common (≥20%) adverse reactions were anemia (25%) and hypothyroidism (23%). The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes (11%), increased GGT (9%), decreased phosphate (6%), decreased sodium (4.7%), increased aspartate aminotransferase (4.4%), increased alkaline phosphatase (4%), decreased hemoglobin (3.6%), increased bilirubin (2.7%), increased glucose (3%), increased triglycerides (2.8%), increased alanine aminotransferase (2.5%), increased magnesium (3.3%), and decreased platelets (2.5%). First line Recurrent or Metastatic Nasopharyngeal Carcinoma Study AK105-304 The safety of penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine was evaluated in Study AK105-304 [see Clinical Studies (14.1) ] . Patients received intravenous placebo or penpulimab-kcqx 200 mg every 3 weeks in combination with 6 cycles of either cisplatin 80 mg/m 2 or carboplatin AUC 5 and gemcitabine 1000 mg/m 2 every 3 weeks followed by placebo or penpulimab-kcqx 200 mg intravenously every 3 weeks until unacceptable toxicity, disease progression or a maximum of 24 months. Among patients who received penpulimab-kcqx, 71% were exposed for 6 months or longer and 38% were exposed for greater than one year. The median age of patients who received penpulimab-kcqx was 51 years (23 to 75 years); 82% were male; 97% were Asian, 3.4% were White; 2.1% were Hispanic or Latino, baseline Eastern Cooperative Oncology Group (ECOG) performance score was 0 (36%) or 1 (64%). Of the 146 patients, 69% of patients had received at least one prior systemic therapy and 100% of patients had received prior radiation therapy. Serious adverse reactions occurred in 51% of patients. The most frequent serious adverse reactions (≥2%) were thrombocytopenia (19%), decreased neutrophils (14%), decreased white blood cells (12%), anemia (8%), myelosuppression (3.4%), decreased sodium (2.7%), pneumonia (2.1%), and nausea (2.1%). Of the patients who received penpulimab-kcqx in combination with either cisplatin or carboplatin and gemcitabine, there was one fatal adverse reaction (0.7%) due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Permanent discontinuation of penpulimab-kcqx due to an adverse reaction occurred in 3.4% of patients. Adverse reactions which resulted in permanent discontinuation of penpulimab-kcqx were acute myocardial infarction, acute kidney injury, brain edema, diabetic ketoacidosis, increased potassium, increased lipase, and thrombocytopenia (0.7% each). Dose interruptions of penpulimab-kcqx due to an adverse reaction occurred in 64% of patients. Adverse reactions which required dose interruption in ≥ 2% of patients included COVID-19 (16%), anemia (16%), thrombocytopenia (14%), decreased white blood cells (14%), decreased neutrophils (10%), pneumonia (10%), increased alanine aminotransferase (3.4%), increased aspartate aminotransferase (2.7%), decreased sodium (2.7%), increased blood creatinine (2.7%), pyrexia (2.1%), and upper respiratory tract infection (2.1%). Table 3 summarizes the adverse reactions in Study AK105-304. Table 3 Adverse Reactions (≥ 10%) in Patients with Recurrent or Metastatic NPC Who Received Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine in Study AK105-304 Adverse Reaction Penpulimab-kcqx Cisplatin or Carboplatin and Gemcitabine N = 146 Placebo Cisplatin or Carboplatin and Gemcitabine N = 142 All Grades 1 (%) Grade 3 or 4 1 (%) All Grades 1 (%) Grade 3 or 4 1 (%) Gastrointestinal disorders Nausea 58 2.1 64 0 Vomiting 2 55 1.4 54 1.4 Constipation 41 0 44 0 Abdominal distension 12 0 6 0 Endocrine disorders Hypothyroidism 3 45 0 27 0 Metabolism and nutrition disorders Decreased appetite 36 0 39 0 Investigations Weight decreased 26 1.4 16 0 Respiratory, thoracic and mediastinal disorders Cough 4 25 0 16 0 Infections and infestations COVID-19 25 0 17 0.7 General disorders and administration site conditions Fatigue 5 25 1.4 22 0 Pyrexia 21 0 20 0.7 Malaise 10 0 8 0 Skin and subcutaneous tissue disorders Rash 6 24 1.4 20 0 Pruritus 11 0 11 0 Nervous system disorders Headache 15 0.7 10 0.7 Dizziness 7 14 0 15 0.7 Renal and urinary disorders Proteinuria 14 0 13 0 Acute kidney injury 8 13 1.4 4.9 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain 9 14 0.7 24 0 Psychiatric disorders Insomnia 12 0 10 0 1 Graded per NCI CTCAE v5.0 2 Includes retching 3 Includes blood thyroid stimulating hormone increased, secondary hypothyroidism 4 Includes productive cough, upper-airway cough syndrome 5 Includes asthenia 6 Includes dermatitis, dermatitis acneiform, drug eruption, eczema, rash maculo-papular, rash papular, rash pustular 7 Includes vertigo 8 Includes acute kidney injury, creatinine renal clearance decreased, glomerular filtration rate decreased, renal failure, renal impairment 9 Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, spinal pain Table 4 summarizes the laboratory abnormalities in AK105-304. Table 4 Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with Recurrent or Metastatic NPC Who Received Penpulimab-kcqx in Combination with Either Cisplatin or Carboplatin and Gemcitabine in Study AK105-304 Laboratory Abnormality Penpulimab-kcqx Cisplatin or Carboplatin /Gemcitabine 2 Placebo Cisplatin or Carboplatin /Gemcitabine 3 All Grades 1 (%) Grade 3 or 4 1 (%) All Grades 1 (%) Grade 3 or 4 1 (%) Hematology White blood cell decreased 99 58 97 58 Hemoglobin decreased 98 49 97 47 Lymphocytes decreased 93 70 89 58 Neutrophils decreased 92 61 95 65 Chemistry Magnesium decreased 69 4.2 58 3.6 Sodium decreased 62 7 58 7 Triglycerides increased 58 4.3 53 4.3 Aspartate aminotransferase increased 52 6 37 2.9 Cholesterol increased 49 2.2 46 0.7 Creatinine increased 48 1.4 39 0.7 Albumin decreased 47 0 44 1.4 Potassium decreased 45 14 31 3.6 Alanine aminotransferase increased 42 8 37 2.1 GGT increased 36 1.4 33 0.7 Alkaline phosphatase increased 32 0.7 30 0 Lipase increased 28 11 23 3.9 Chloride decreased 25 1.4 11 0 Serum amylase increased 23 2.9 17 0.7 Glucose decreased 22 1.4 20 0.7 Lipids increased 21 1.4 20 0.7 1 Toxicity graded according to NCI CTCAE v5.0. 2 The denominator used to calculate the rate varied from 102 to 146 based on the number of patients with a baseline value and at least one post-treatment value. 3 The denominator used to calculate the rate varied from 103 to 142 based on the number of patients with a baseline value and at least one post-treatment value. Recurrent Metastatic Non-Keratinizing Nasopharyngeal Carcinoma Study AK105-202 The safety of penpulimab-kcqx as a single agent was evaluated in Study AK105-202 [see Clinical Studies (14.2) ]. Eligible patients had metastatic non-keratinizing NPC and had received prior platinum-based chemotherapy and at least one other line of therapy or had disease progression within 6 months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment. Patients received penpulimab-kcqx 200 mg intravenously every 2 weeks until unacceptable toxicity, disease progression, or a maximum of 24 months. Among patients who received penpulimab-kcqx, 45% were exposed for 6 months or longer and 30% for exposed for greater than one year. The median age of patients who received penpulimab-kcqx was 50 years (20 to 66 years); 76% were male; 100% were Asian, 100% had recurrent disease; baseline Eastern Cooperative Oncology Group (ECOG) performance score was 0 (31%) or 1 (69%). All patients had received at least one prior systemic therapy and prior radiation. Serious adverse reactions occurred in 22% of patients. Serious adverse reactions in ≥1% were pneumonia (3.8%), pneumonitis (1.5%), respiratory failure (1.5%), rash (1.5%). Fatal adverse reactions occurred in 1% of patients treated with penpulimab-kcqx, including a case each of pneumonitis, septic shock, colitis, and hepatitis. Permanent discontinuation of penpulimab-kcqx due to an adverse reaction occurred in 3.8% of patients. Adverse reactions which resulted in permanent discontinuation of penpulimab-kcqx in ≥1% were rash, hepatitis, herpes zoster, spinal cord compression and pleural effusion (0.8% each). Dose interruptions of penpulimab-kcqx due to an adverse reaction occurred in 25% of patients. Adverse reactions which required dose interruption in ≥ 1% of patients included hepatitis (6.2%), anemia (3.1%), pneumonia (3.1%), hypothyroidism (3.1%), rash (1.5%) and white blood cells decreased (1.5%). Table 5 summarizes the adverse reactions in AK105-202. Table 5 Adverse Reactions (≥ 10%) in Patients with Recurrent Metastatic Non-Keratinizing NPC Who Received Penpulimab-kcqx in Study AK105-202 Adverse Reaction Penpulimab-kcqx N = 130 All Grades 1 (%) Grade 3 or 4 1 (%) Endocrine disorders Hypothyroidism 2 39 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain 3 25 0.8 Investigations Weight decreased 19 1.5 General disorders and administration site conditions Pyrexia 15 0 Infections and infestations Upper respiratory tract infection 13 0.8 Respiratory, thoracic and mediastinal disorders Cough 4 11 0 Skin and subcutaneous tissue disorders Rash 5 11 2.3 1 Graded per NCI CTCAE v5.0 2 Includes blood thyroid stimulating hormone increased 3 Includes arthralgia, back pain, bone pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, pain in extremity 4 Includes productive cough 5 Includes dermatitis acneiform, eczema, pemphigoid Table 6 summarizes the laboratory abnormalities in AK105-202. Table 6 Select Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients with Recurrent Metastatic Non-Keratinizing NPC Who Received Penpulimab-kcqx in Study AK105-202 Laboratory Abnormality Penpulimab-kcqx All Grades 1 (%) 2 Grades 3 or 4 (%) Chemistry Creatinine increased 81 0 Phosphate decreased 47 8 Sodium decreased 46 6 Albumin decreased 45 0 Triglycerides increased 38 3.1 Alkaline phosphatase increased 35 5 Aspartate aminotransferase increased 33 3.9 GGT increased 34 8 Glucose increased 34 0 Magnesium decreased 28 0.8 Activated partial thromboplastin time prolonged 22 0 Alanine aminotransferase increased 20 3.9 Hematology Lymphocytes decreased 43 16 Hemoglobin decreased 36 4.7 1 Toxicity graded according to NCI CTCAE v5.0. 2 Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: penpulimab-kcqx (range of the patient number: 128 to130).

<table width="100%" cellspacing="0" cellpadding="0"><tbody><tr><td rowspan="2" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td colspan="2" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Penpulimab-kcqx Cisplatin or Carboplatin and Gemcitabine N = 146 </content></paragraph></td><td colspan="2" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Placebo Cisplatin or Carboplatin and Gemcitabine N = 142 </content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">All Grades ¹ (%) </content></paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Grade 3 or 4 ¹ (%) </content></paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">All Grades ¹ (%) </content></paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Grade 3 or 4 ¹ (%) </content></paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Nausea</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>58</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>2.1</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>64</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Vomiting ²</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>55</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>54</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Constipation</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>41</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>44</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Abdominal distension</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>12</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>6</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Hypothyroidism ³</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>45</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>27</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Decreased appetite</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>36</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>39</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Investigations</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Weight decreased</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>26</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>16</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Cough ⁴</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>25</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>16</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Infections and infestations</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>COVID-19</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>25</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>17</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Fatigue ⁵</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>25</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>22</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Pyrexia</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>21</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>20</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Malaise</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>10</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>8</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Rash ⁶</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>24</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>20</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Pruritus</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>11</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>11</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Headache</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>15</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>10</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Dizziness ⁷</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>14</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>15</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Renal and urinary disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Proteinuria</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>14</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>13</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Acute kidney injury ⁸</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>13</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.4</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>4.9</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Musculoskeletal pain ⁹</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>14</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.7</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>24</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="5" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Insomnia</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>12</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>10</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr></tbody></table>

<table width="99%" cellspacing="0" cellpadding="0" border="1"><tbody><tr><td styleCode="Lrule Rrule Toprule Botrule"><content styleCode="bold">Laboratory Abnormality</content></td><td rowspan="1" colspan="2" styleCode="Lrule Rrule Toprule Botrule">Penpulimab-kcqx Cisplatin or Carboplatin /Gemcitabine ²</td><td rowspan="1" colspan="2" styleCode="Lrule Rrule Toprule Botrule">Placebo Cisplatin or Carboplatin /Gemcitabine ³</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule">All Grades ¹ (%) </td><td styleCode="Lrule Rrule Toprule Botrule">Grade 3 or 4 ¹ (%) </td><td styleCode="Lrule Rrule Toprule Botrule">All Grades ¹ (%) </td><td styleCode="Lrule Rrule Toprule Botrule">Grade 3 or 4 ¹ (%) </td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><content styleCode="bold">Hematology</content></td><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">White blood cell decreased</td><td styleCode="Lrule Rrule Toprule Botrule">99</td><td styleCode="Lrule Rrule Toprule Botrule">58</td><td styleCode="Lrule Rrule Toprule Botrule">97</td><td styleCode="Lrule Rrule Toprule Botrule">58</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Hemoglobin decreased</td><td styleCode="Lrule Rrule Toprule Botrule">98</td><td styleCode="Lrule Rrule Toprule Botrule">49</td><td styleCode="Lrule Rrule Toprule Botrule">97</td><td styleCode="Lrule Rrule Toprule Botrule">47</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Lymphocytes decreased</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule">93</td><td styleCode="Lrule Rrule Toprule Botrule">70</td><td styleCode="Lrule Rrule Toprule Botrule">89</td><td styleCode="Lrule Rrule Toprule Botrule">58</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Neutrophils decreased</td><td styleCode="Lrule Rrule Toprule Botrule">92</td><td styleCode="Lrule Rrule Toprule Botrule">61</td><td styleCode="Lrule Rrule Toprule Botrule">95</td><td styleCode="Lrule Rrule Toprule Botrule">65</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><content styleCode="bold">Chemistry</content></td><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/><td styleCode="Lrule Rrule Toprule Botrule"/></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Magnesium decreased</td><td styleCode="Lrule Rrule Toprule Botrule">69</td><td styleCode="Lrule Rrule Toprule Botrule">4.2</td><td styleCode="Lrule Rrule Toprule Botrule">58</td><td styleCode="Lrule Rrule Toprule Botrule">3.6</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Sodium decreased</td><td styleCode="Lrule Rrule Toprule Botrule">62</td><td styleCode="Lrule Rrule Toprule Botrule">7</td><td styleCode="Lrule Rrule Toprule Botrule">58</td><td styleCode="Lrule Rrule Toprule Botrule">7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Triglycerides increased</td><td styleCode="Lrule Rrule Toprule Botrule">58</td><td styleCode="Lrule Rrule Toprule Botrule">4.3</td><td styleCode="Lrule Rrule Toprule Botrule">53</td><td styleCode="Lrule Rrule Toprule Botrule">4.3</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Aspartate aminotransferase increased</td><td styleCode="Lrule Rrule Toprule Botrule">52</td><td styleCode="Lrule Rrule Toprule Botrule">6</td><td styleCode="Lrule Rrule Toprule Botrule">37</td><td styleCode="Lrule Rrule Toprule Botrule">2.9</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Cholesterol increased</td><td styleCode="Lrule Rrule Toprule Botrule">49</td><td styleCode="Lrule Rrule Toprule Botrule">2.2</td><td styleCode="Lrule Rrule Toprule Botrule">46</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Creatinine increased</td><td styleCode="Lrule Rrule Toprule Botrule">48</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td><td styleCode="Lrule Rrule Toprule Botrule">39</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Albumin decreased</td><td styleCode="Lrule Rrule Toprule Botrule">47</td><td styleCode="Lrule Rrule Toprule Botrule">0</td><td styleCode="Lrule Rrule Toprule Botrule">44</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Potassium decreased</td><td styleCode="Lrule Rrule Toprule Botrule">45</td><td styleCode="Lrule Rrule Toprule Botrule">14</td><td styleCode="Lrule Rrule Toprule Botrule">31</td><td styleCode="Lrule Rrule Toprule Botrule">3.6</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Alanine aminotransferase increased</td><td styleCode="Lrule Rrule Toprule Botrule">42</td><td styleCode="Lrule Rrule Toprule Botrule">8</td><td styleCode="Lrule Rrule Toprule Botrule">37</td><td styleCode="Lrule Rrule Toprule Botrule">2.1</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">GGT increased</td><td styleCode="Lrule Rrule Toprule Botrule">36</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td><td styleCode="Lrule Rrule Toprule Botrule">33</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Alkaline phosphatase increased</td><td styleCode="Lrule Rrule Toprule Botrule">32</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td><td styleCode="Lrule Rrule Toprule Botrule">30</td><td styleCode="Lrule Rrule Toprule Botrule">0</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Lipase increased</td><td styleCode="Lrule Rrule Toprule Botrule">28</td><td styleCode="Lrule Rrule Toprule Botrule">11</td><td styleCode="Lrule Rrule Toprule Botrule">23</td><td styleCode="Lrule Rrule Toprule Botrule">3.9</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Chloride decreased</td><td styleCode="Lrule Rrule Toprule Botrule">25</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td><td styleCode="Lrule Rrule Toprule Botrule">11</td><td styleCode="Lrule Rrule Toprule Botrule">0</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Serum amylase increased</td><td styleCode="Lrule Rrule Toprule Botrule">23</td><td styleCode="Lrule Rrule Toprule Botrule">2.9</td><td styleCode="Lrule Rrule Toprule Botrule">17</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Glucose decreased</td><td styleCode="Lrule Rrule Toprule Botrule">22</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td><td styleCode="Lrule Rrule Toprule Botrule">20</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule">Lipids increased</td><td styleCode="Lrule Rrule Toprule Botrule">21</td><td styleCode="Lrule Rrule Toprule Botrule">1.4</td><td styleCode="Lrule Rrule Toprule Botrule">20</td><td styleCode="Lrule Rrule Toprule Botrule">0.7</td></tr></tbody></table>

<table width="100%" cellspacing="0" cellpadding="0"><tbody><tr><td rowspan="2" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td colspan="2" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Penpulimab-kcqx N = 130 </content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">All Grades ¹</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Grade 3 or 4 ¹</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Endocrine disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Hypothyroidism ²</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>39</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Musculoskeletal pain ³</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>25</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.8</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Investigations</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Weight decreased</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>19</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>1.5</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Pyrexia</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>15</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Infections and infestations</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Upper respiratory tract infection</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>13</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0.8</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Cough ⁴</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>11</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>0</paragraph></td></tr><tr><td colspan="3" styleCode="Lrule Rrule Toprule Botrule"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>Rash ⁵</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>11</paragraph></td><td styleCode="Lrule Rrule Toprule Botrule"><paragraph>2.3</paragraph></td></tr></tbody></table>