6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling.

•: Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)].
•: Infusion-Related Reactions [see Warnings and Precautions (5.2)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described in the WARNINGS AND PRECAUTIONS section reflect exposure to IMFINZI as a single agent in a total of 1,889 patients enrolled in the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with unresectable Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 970 patients with advanced solid tumors), and an additional open-label, single-arm study (ATLANTIC Study) that enrolled 444 patients with advanced solid tumors, including NSCLC. In these studies, IMFINZI was administered at a dose of 10 mg/kg every 2 weeks. Among the 1889 patients, 38% were exposed for 6 months or more and 18% were exposed for 12 months or more. The data also reflect exposure to IMFINZI 1,500 mg every 4 weeks as a single agent in 262 patients from the ADRIATIC study (a randomized, double-blind study in patients with LS-SCLC) and to IMFINZI in combination with chemotherapy in 265 patients from the CASPIAN study (a randomized, open-label study in patients with ES-SCLC) and in 338 patients from the TOPAZ 1 study (a randomized, double-blind study in patients with BTC). In the CASPIAN and TOPAZ 1 studies, IMFINZI was administered at a dose of 1,500 mg every 3 or 4 weeks.

The data also reflect exposure to IMFINZI 1,120 mg in combination with carboplatin and paclitaxel (every 3 weeks for up to 6 cycles) followed by IMFINZI 1,500 mg (every 4 weeks) as a single agent in 235 patients in DUO-E (a randomized, placebo-controlled trial in endometrial cancer). Among the 235 patients, 77% (181 patients) were exposed to IMFINZI for 6 months or more and 41% (96 patients) for 12 months or more.

The data also reflect exposure to IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg in 388 patients in HIMALAYA. In the HIMALAYA study patients received IMFINZI 1,500 mg in combination with tremelimumab-actl as a single intravenous infusion of 300 mg, followed by IMFINZI 1,500 mg every 4 weeks. The pooled safety population (N = 596) described in the WARNINGS AND PRECAUTIONS section reflect exposure to IMFINZI 1,500 mg in combination with tremelimumab-actl 75 mg and histology-based platinum chemotherapy regimens in 330 patients in POSEIDON [see Clinical Studies (14.1)], and 266 patients with ES-SCLC in CASPIAN who received up to four cycles of platinum-etoposide plus IMFINZI 1,500 mg with tremelimumab-actl 75 mg every 3 weeks, followed by IMFINZI 1,500 mg every 4 weeks (an unapproved regimen for extensive stage small cell lung cancer). Among the 596 patients, 55% were exposed to IMFINZI for 6 months or more and 24% were exposed for 12 months or more.

The data described in this section reflect exposure to IMFINZI in patients with unresectable Stage III NSCLC enrolled in the PACIFIC study, in patients with metastatic NSCLC enrolled in the POSEIDON study, in patients with LS-SCLC enrolled in the ADRIATIC study, in patients with ES-SCLC enrolled in the CASPIAN study, in patients with BTC enrolled in the TOPAZ-1 study, in patients with uHCC included in the HIMALAYA study, in patients with dMMR endometrial cancer enrolled in the DUO-E study, and in patients with resectable NSCLC enrolled in the AEGEAN study.

Non-Small Cell Lung Cancer

Neoadjuvant and Adjuvant Treatment of Resectable NSCLC – AEGEAN

The safety of IMFINZI in combination with neoadjuvant platinum-containing chemotherapy followed by surgery, and continued adjuvant treatment with IMFINZI as a single agent after surgery, was investigated in AEGEAN, a randomized, double-blind, placebo-controlled, multicenter study for patients with resectable NSCLC (Stage IIA to select Stage IIIB [AJCC, 8th edition]); squamous or non-squamous) [see Clinical Studies (14.1)].

Safety data are available for the 799 patients who received IMFINZI in combination with chemotherapy (n=401) or placebo in combination with chemotherapy (n=398).

The median duration of exposure to IMFINZI 1,500 mg every 3 weeks in the neoadjuvant phase was 12 weeks (range: 0 to 19 weeks). The median duration of exposure to IMFINZI 1,500 mg every 4 weeks in the adjuvant phase was 37 weeks (range: 4 to 67 weeks). The median age of patients who received IMFINZI was 65 years (range: 30 to 88), 52% age 65 or older, 12% age 75 or older; 65% male; 54% White, 41% Asian, 1% Black, 3% Other races; and 17% Hispanic or Latino.

The most common adverse reactions (occurring in ≥ 20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.

Table 5 summarizes the adverse reactions that occurred in (≥ 10%) patients treated with IMFINZI in combination with chemotherapy.

Table 5. Adverse Reactions Occurring in ≥ 10% of Patients in the AEGEAN Study
Adverse Reaction	IMFINZI with Chemotherapy N=401		Placebo with Chemotherapy N=398
Adverse Reaction	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
* includes colitis, diarrhea, enteritis, and proctitis. † includes fatigue and asthenia. ‡ includes dermatitis, dermatitis acneiform, drug eruption, eczema, eczema asteatotic, erythema, palmar‑erythrodysaesthesia syndrome, pemphigoid, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular, skin exfoliation, and urticarial dermatitis. § includes arthralgia, arthritis, back pain, bone pain, chest pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal discomfort, musculoskeletal stiffness,myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. ¶ includes dysaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, paraesthesia, peripheral sensory neuropathy, and polyneuropathy. # includes blood thyroid stimulating hormone increased and hypothyroidism. Þ includes lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia chlamydial, pneumonia cryptococcal, pneumonia fungal, pneumonia pseudomonal, pneumonia streptococcal, pneumonia viral, and post-procedural pneumonia. ß Five Grade 5 events in the IMFINZI arm and four Grade 5 events in the Placebo arm. à Includes COVID-19 and COVID-19 Pneumonia. Five Grade 5 events in the IMFINZI arm and One Grade 5 event in the placebo arm.
Gastrointestinal disorders
Nausea	25	0.2	29	0.3
Constipation	25	0.2	21	0
Diarrhea*	14	1.0	13	1.3
Vomiting	11	0.7	11	1.0
General disorders and administration site conditions
Fatigue†	25	0	25	1.5
Skin and subcutaneous tissue disorders
Rash‡	22	0.5	14	0.3
Pruritus	12	0.2	6	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain§	24	1.0	29	0.5
Metabolism and nutrition disorders
Decreased appetite	18	0.2	18	0.3
Nervous system disorders
Peripheral neuropathy¶	16	0.5	22	0.8
Endocrine disorders
Hypothyroidism#	11	0	3.8	0
Respiratory, thoracic and mediastinal disorders
Cough / Productive cough	11	0	13	0
PneumoniaÞ, ß	11	3.5	10	3.0
COVID-19à	11	0.2	9	0.8
Psychiatric Disorders
Insomnia	10	0	12	0

Table 6 summarizes the laboratory abnormalities in patients treated with IMFINZI in combination with chemotherapy.

Table 6. Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with Disease Who Received IMFINZI with Chemotherapy in AEGEAN
* Graded per NCI CTCAE V5. † The denominator used to calculate the rate varied from 349 to 399 based on the number of patients with a baseline value and at least one post-treatment value. ‡ The denominator used to calculate the rate varied from 333 to 398 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality*	IMFINZI with Chemotherapy†		Placebo with Chemotherapy‡
Laboratory Abnormality*	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
Hematology
Hemoglobin decreased	78	10	75	9
Leukocytes decreased	63	12	64	11
Neutrophils decreased	52	24	56	27
Platelets decreased	46	7	44	8
Lymphocytes decreased	41	11	37	9
Chemistry
Calcium corrected, decreased	51	3.3	52	4.5
Alanine aminotransferase increased	49	6	42	2
Aspartate aminotransferase increased	47	3.5	37	1.8
Potassium increased	33	1.5	29	2
Sodium decreased	35	5	33	6
Gamma glutamyl transferase increased	36	4.7	35	2.1
Creatinine increased	32	2.3	27	3.3
Amylase increased	25	4.7	24	3.6
Magnesium decreased	22	2.8	20	3.6
Lipase increased	23	4.9	24	7

Neoadjuvant Phase of AEGEAN

A total of 401 patients received at least 1 dose of IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment and 398 patients received at least 1 dose of placebo in combination with platinum-containing chemotherapy as neoadjuvant treatment.

Serious adverse reactions occurred in 21% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%).

Permanent discontinuation of any study drug due to an adverse reaction occurred in 14% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (>0.5%) adverse reactions that led to permanent discontinuation of any study drug were anemia (1.5%), neutropenia (0.7%), myelosuppression (0.7%), and periphery sensory neuropathy (0.7%). Permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥0.5%) adverse reactions that led to permanent discontinuation of IMFINZI were peripheral sensory neuropathy (0.7%) and pneumonitis (0.5%).

Of the 401 IMFINZI-treated patients and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions. Adverse reactions that led to cancellation of surgery in the IMFINZI arm were COVID-19 pneumonia, HIV infection, pneumonitis, prostate cancer, colon cancer, pruritus, and colitis.

Of the 325 IMFINZI-treated patients who received surgery, 4% (n=15) experienced delay of surgery (a surgical delay is defined as on-study surgery occurring more than 40 days after the last dose of study treatment in the neoadjuvant period) due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 4% (n=16) experienced delay of surgery due to adverse reactions.

Of the 325 IMFINZI-treated patients who received surgery, 6.5% (n=21) did not receive adjuvant treatment due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 5.8% (n=19) did not receive adjuvant treatment due to adverse reactions.

Adjuvant Phase of AEGEAN

A total of 265 patients in the IMFINZI arm and 254 patients in the placebo arm received at least 1 dose of adjuvant treatment.

Of the patients who received single agent IMFINZI as adjuvant treatment, 13% experienced serious adverse reactions. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. Permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 8% of patients. The most frequent (≥0.5%) adverse reaction that led to permanent discontinuation of adjuvant IMFINZI was pneumonitis (1.1%) and rash (0.8%).

Unresectable Stage III NSCLC - PACIFIC

The safety of IMFINZI in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. A total of 475 patients received IMFINZI 10 mg/kg intravenously every 2 weeks. The study excluded patients who had disease progression following chemoradiation, with active or prior autoimmune disease within 2 years of initiation of the study or with medical conditions that required systemic immunosuppression [see Clinical Studies (14.1)].

The study population characteristics were: median age of 64 years (range: 23 to 90), 45% age 65 years or older, 70% male, 69% White, 27% Asian, 75% former smoker, 16% current smoker, and 51% had WHO performance status of 1. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy. The median duration of exposure to IMFINZI was 10 months (range: 0.2 to 12.6).

IMFINZI was discontinued due to adverse reactions in 15% of patients. The most common adverse reactions leading to IMFINZI discontinuation were pneumonitis or radiation pneumonitis in 6% of patients. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in < 2% of patients and were similar across arms. The most common adverse reactions (occurring in ≥ 20% of patients) were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

Table 7 summarizes the adverse reactions that occurred in at least 10% of patients treated with IMFINZI.

Table 7. Adverse Reactions Occurring in ≥ 10% of Patients in the PACIFIC Study
* Includes acute interstitial pneumonitis, interstitial lung disease, pneumonitis, pulmonary fibrosis. † Includes dyspnea, and exertional dyspnea. ‡ Includes asthenia and fatigue. § Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection. ¶ Includes lung infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia klebsiella, pneumonia necrotizing, pneumonia pneumococcal, and pneumonia streptococcal. # Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash, and dermatitis. Þ Includes pruritus generalized and pruritus. ß Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain. à Includes autoimmune hypothyroidism and hypothyroidism.
	IMFINZI N = 475		Placebo N = 234
Adverse Reaction	All Grades (%)	Grades 3-4 (%)	All Grades (%)	Grades 3-4 (%)
Respiratory, Thoracic, and Mediastinal Disorders
Cough/Productive Cough	40	0.6	30	0.4
Pneumonitis*/Radiation Pneumonitis	34	3.4	25	3
Dyspnea†	25	1.5	25	2.6
General Disorders
Fatigue‡	34	0.8	32	1.3
Pyrexia	15	0.2	9	0
Infections
Upper respiratory tract infections§	26	0.4	19	0
Pneumonia¶	17	7	12	6
Skin and Subcutaneous Tissue Disorders
Rash#	23	0.6	12	0
PruritusÞ	12	0	6	0
Gastrointestinal Disorders
Diarrhea	18	0.6	19	1.3
Abdominal painß	10	0.4	6	0.4
Endocrine Disorders
Hypothyroidismà	12	0.2	1.7	0

Other adverse reactions occurring in less than 10% of patients treated with IMFINZI were dysphonia, dysuria, night sweats, peripheral edema, and increased susceptibility to infections.

Table 8 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI.

Table 8. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the PACIFIC Study
* Graded according to NCI CTCAE version 4.0. † Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 464 to 470) and placebo (range: 224 to 228).
	IMFINZI		Placebo
Laboratory Abnormality	All Grades* (%)†	Grade 3 or 4 (%)	All Grades* (%)†	Grade 3 or 4 (%)
Chemistry
Hyperglycemia	52	8	51	8
Hypocalcemia	46	0.2	41	0
Increased ALT	39	2.3	22	0.4
Increased AST	36	2.8	21	0.4
Hyponatremia	33	3.6	30	3.1
Hyperkalemia	32	1.1	29	1.8
Increased GGT	24	3.4	22	1.7
Hematology
Lymphopenia	43	17	39	18

Metastatic NSCLC - POSEIDON

The safety of IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy in patients with metastatic NSCLC was evaluated in POSEIDON (NCT03164616), a randomized, open-label, multicenter, active-controlled trial. A total of 330 patients received IMFINZI 1,500 mg in combination with tremelimumab-actl (≥ 30 kg body weight received 75 mg and < 30 kg body weight received 1 mg/kg) and histology-based platinum chemotherapy regimens [see Clinical Studies (14.1)]. Of these patients, 66% received the maximum 5 doses of tremelimumab-actl and 79% received at least 4 doses. Treatment was continued with IMFINZI as a single agent (or with IMFINZI and histologically-based pemetrexed for non-squamous patients based on the investigator’s decision) until disease progression or unacceptable toxicity. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.1)].

The median age of patients who received IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy was 63 years (range: 27 to 87); 80% male; 61% White, 29% Asian, 58% former smoker, 25% current smoker, and 68% ECOG performance of 1.

Serious adverse reactions occurred in 44% of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy. These include hepatitis, nephritis, myocarditis, pancreatitis (all in the same patient), death (2 patients), sepsis (2 patients), pneumonitis (2 patients), acute kidney injury (2 patients), febrile neutropenia (1 patient), chronic obstructive pulmonary disease (COPD) (1 patient), dyspnea (1 patient), sudden death (1 patient), and ischemic stroke (1 patient).

Permanent discontinuation of IMFINZI or tremelimumab-actl due to an adverse reaction occurred in 17% of the patients. Adverse reactions which resulted in permanent discontinuation of IMFINZI or tremelimumab-actl in > 2% of patients included pneumonia.

Dosage interruption or delay of IMFINZI and tremelimumab-actl due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption or delay of IMFINZI and tremelimumab-actl in > 1% of patients included anemia, leukopenia/white blood cell count decreased, pneumonia, pneumonitis, colitis, diarrhea, hepatitis, rash, asthenia, amylase increased, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, neutropenia/ neutrophil count decreased, and thrombocytopenia/platelet count decreased.

The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia and thrombocytopenia.

Table 9 summarizes the adverse reactions in POSEIDON.

Table 9. Adverse Reactions (≥ 10%) in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study
* Includes mucosal inflammation and stomatitis. † Includes asthenia and fatigue. ‡ Includes body temperature increased, hyperpyrexia, hyperthermia, and pyrexia. § Includes face edema, localized edema, and edema peripheral. ¶ Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, and spinal pain. # Includes eczema, erythema, dermatitis, drug eruption, erythema multiforme, pemphigoid, rash, rash maculo-papular, rash papular, rash pruritic, and rash pustular. Þ Includes lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia aspiration, and pneumonia bacterial. ß Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis and upper respiratory tract infection. à Includes blood thyroid stimulating hormone increased and hypothyroidism. è Includes cough and productive cough. ð Includes headache and migraine.
	IMFINZI with tremelimumab-actl and platinum-based chemotherapy N = 330		Platinum-based chemotherapy N = 333
Adverse Reaction	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
Gastrointestinal disorders
Nausea	42	1.8	37	2.1
Diarrhea	22	1.5	15	1.5
Constipation	19	0	24	0.6
Vomiting	18	1.2	14	1.5
Stomatitis*	10	0	6	0.3
General disorders and administration site conditions
Fatigue/Asthenia†	36	5	32	4.5
Pyrexia‡	19	0	8	0
Edema§	10	0	10	0.6
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain¶	29	0.6	22	1.5
Metabolism and nutrition disorders
Decreased appetite	28	1.5	25	1.2
Skin and subcutaneous tissue disorders
Rash#	27	2.4	10	0.6
Pruritus	11	0	4.5	0
Alopecia	10	0	6	0
Infections and Infestations
PneumoniaÞ	17	8	12	4.2
Upper respiratory tract infectionsß	15	0.6	9	0.9
Endocrine disorders
Hypothyroidismà	13	0	2.1	0
Respiratory, thoracic and mediastinal disorders
Cough/Productive Coughè	12	0	8	0.3
Nervous system disorders
Headacheð	11	0	8	0.6

Table 10 summarizes the laboratory abnormalities in POSEIDON.

Table 10. Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with NSCLC Who Received IMFINZI in the POSEIDON Study
* Graded according to NCI CTCAE version 4.03. † The denominator used to calculate the rate varied from 45 to 326 based on the number of patients with a baseline value and at least one post-treatment value. ‡ The denominator used to calculate the rate varied from 43 to 323 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality*	IMFINZI with tremelimumab-actl and platinum-based chemotherapy†		Platinum-based chemotherapy‡
Laboratory Abnormality*	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
Chemistry
Blood creatinine increased	89	4	83	1.9
Increased ALT	64	6	56	4.7
Increased AST	63	5	55	2.2
Hypocalcemia	58	0.9	49	0.9
Hyponatremia	55	13	50	11
Hyperkalemia	49	2.2	35	2.8
Hyperglycemia	42	6	37	3.1
Amylase increased	41	9	25	6
Gamma Glutamyl Transferase increased	38	2.2	35	4.7
Lipase increased	35	14	25	5
Increased Alkaline Phosphatase	33	3.4	26	1.2
Albumin decreased	27	1.9	18	0.9
Hypokalemia	21	7	17	2.8
Bilirubinemia	16	0.9	8	0.3
Hypernatremia	15	0	14	0
Hypomagnesemia	12	4	23	0
Hematology
Anemia	84	24	84	25
Leukopenia	77	21	81	18
Neutropenia	71	37	69	32
Lymphocytopenia	67	20	60	19
Thrombocytopenia	53	11	54	12

Small Cell Lung Cancer

Limited Stage Small Cell Lung Cancer – ADRIATIC

The safety of IMFINZI as a single agent in patients with LS-SCLC without disease progression following completion of concurrent platinum-based chemoradiotherapy (60-66 Gy once daily over 6 weeks or 45 Gy twice daily over 3 weeks) within 42 days prior to initiation of study drug, was evaluated in the ADRIATIC study, a multicenter, randomized, double-blind, placebo-controlled study [see Clinical Studies (14.2)]. A total of 262 patients received IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity or a maximum of 24 months. The study excluded patients with Stage I or II LS-SCLC who were considered medically operable and patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants.

The study population characteristics were: median age of 62 years (range: 28 to 84); 39% age 65 years or older, 6% age 75 years or older; 69% male; 50% white, 48% Asian, 1.3% other races; 4.2% Hispanic or Latino; 68% former smoker, 22% current smoker; and 51% had WHO performance status of 1. Sixty-seven percent of patients received a total radiation dose of 60 Gy to 66 Gy once daily and 27% of patients received a total radiation dose of 45 Gy twice daily. The median duration of exposure to IMFINZI was 9.2 months (range: 0.92 to 25) in the IMFINZI arm.

Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥ 1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each). Permanent discontinuation of IMFINZI due to adverse reactions occurred in 16% of the patients. Adverse reactions which resulted in permanent discontinuation of IMFINZI in ≥ 1% of patients included pneumonitis or radiation pneumonitis (9%) and pneumonia (1.5%). Dosage interruptions of IMFINZI due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients included pneumonitis or radiation pneumonitis (17%). The most common adverse reactions occurring in ≥ 20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%).

Table 11 summarizes the adverse reactions that occurred in patients treated with IMFINZI in the ADRIATIC study.

Table 11. Adverse Reactions (≥ 10%) in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study
	IMFINZI (n=262)		Placebo (n=265)
Adverse Reaction	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
* Includes pneumonitis, immune-mediated lung disease, interstitial lung disease, radiation pneumonitis, and lung radiation fibrosis † Includes dyspnea and exertional dyspnea. ‡ Includes fatigue and asthenia. § Includes dermatitis, acneiform dermatitis, eczema, rash, maculo-papular rash, papular rash, pruritic rash, and skin exfoliation. ¶ Includes hypothyroidism, increased blood thyroid stimulating hormone, and decreased thyroxine free. # Includes hyperthyroidism, decreased blood thyroid stimulating hormone, increased thyroxine free, increased thyroxine, increased tri-iodothyronine free, and increased tri-iodothyronine. Þ Includes dizziness, postural dizziness, vertigo, and positional vertigo. ß Includes pneumonia, atypical pneumonia, lower respiratory tract infection, bacterial pneumonia, pneumocystis jirovecii pneumonia, legionella pneumonia, and viral pneumonia.
Respiratory, thoracic and mediastinal disorders
Pneumonitis or Radiation pneumonitis*	38	3.1	30	2.6
Cough/Productive cough	17	0	14	0
Dyspnea†	11	0.4	7	0
General disorders
Fatigue‡	21	0.4	20	2.3
Skin and subcutaneous tissue disorders
Rash§	18	0.4	11	0
Pruritus	13	0	7	0
Endocrine disorders
Hypothyroidism¶	17	0	4.9	0
Hyperthyroidism#	12	0	1.9	0
Metabolism and nutrition disorders
Decreased appetite	17	0	13	0
Nervous system disorders
DizzinessÞ	14	0	9	0
Infections and infestations
Pneumoniaß	13	3.1	9	4.2
Gastrointestinal disorders
Nausea	13	0	11	0
Diarrhea	11	1.9	8	0
Constipation	10	0	10	0

Table 12 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI.

Table 12. Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with LS-SCLC Who Received IMFINZI in the ADRIATIC Study
Laboratory Abnormality*	IMFINZI†		Placebo‡
Laboratory Abnormality*	All Grades (%)	Grade 3 or 4 (%)	All Grades (%)	Grade 3 or 4 (%)
* Graded according to NCI CTCAE version 4.03, except creatinine increased which is graded according to NCI CTCAE version 5.0. † The denominator used to calculate the rate varied from 63 to 259 based on the number of patients with a baseline value and at least one post-treatment value. ‡ The denominator used to calculate the rate varied from 65 to 262 based on the number of patients with a baseline value and at least one post-treatment value.
Chemistry
Hypocalcemia	43	0	43	0.8
Hyperglycemia	38	3.2	45	1.5
ALT increased	36	2.3	29	2.3
AST increased	33	2.3	28	1.5
Gamma Glutamyl Transferase increased	32	7	27	2.9
Hyponatremia	32	5	29	6.2
Hyperkalemia	23	1.2	17	0.8
Creatinine increased*	21	0	17	0.8
Hematology
Lymphocytes decreased	34	10	33	10
Leukocytes decreased	26	0.4	33	1.1

Extensive Stage Small Cell Lung Cancer – CASPIAN

The safety of IMFINZI in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was evaluated in CASPIAN, a randomized, open-label, multicenter, active-controlled study. A total of 265 patients received IMFINZI 1,500 mg in combination with chemotherapy every 3 weeks for 4 cycles followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. The stydy excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies (14.2)]. Among 265 patients receiving IMFINZI, 49% were exposed for 6 months or longer and 19% were exposed for 12 months or longer.

Among 266 patients receiving chemotherapy alone, 57% of the patients received 6 cycles of chemotherapy and 8% of the patients received prophylactic cranial irradiation (PCI) after chemotherapy.

IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. These include pneumonitis, hepatotoxicity, neurotoxicity, sepsis, diabetic ketoacidosis and pancytopenia (1 patient each). Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients). The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue/asthenia and alopecia.

Table 13 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy.

Table 13. Adverse Reactions Occurring in ≥ 10% of Patients in the CASPIAN Study
* Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash and dermatitis. † Includes hyperthyroidism and Basedow's disease.
	IMFINZI with etoposide and either carboplatin or cisplatin N = 265		Etoposide and either carboplatin or cisplatin N = 266
Adverse Reaction	All Grades (%)	Grade 3-4 (%)	All Grades (%)	Grade 3-4 (%)
Gastrointestinal disorders
Nausea	34	0.4	34	1.9
Constipation	17	0.8	19	0
Vomiting	15	0	17	1.1
Diarrhea	10	1.1	11	1.1
General disorders and administration site conditions
Fatigue/Asthenia	32	3.4	32	2.3
Skin and subcutaneous tissue disorders
Alopecia	31	1.1	34	0.8
Rash*	11	0	6	0
Metabolism and nutrition disorders
Decreased appetite	18	0.8	17	0.8
Respiratory, thoracic and mediastinal disorders
Cough/Productive Cough	15	0.8	9	0
Endocrine disorders
Hyperthyroidism†	10	0	0.4	0

Table 14 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI plus chemotherapy.

Table 14. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20%* of Patients in the CASPIAN study
* The frequency cut off is based on any grade change from baseline. † Graded according to NCI CTCAE version 4.03. ‡ Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 258 to 263) and chemotherapy (range: 253 to 262) except magnesium IMFINZI with chemotherapy (18) and chemotherapy (16). § LLN = lower limit of normal.
	IMFINZI with Etoposide and either Carboplatin or Cisplatin	Etoposide and either Carboplatin or Cisplatin
Laboratory Abnormality	Grade† 3 or 4 (%)‡	Grade† 3 or 4 (%)‡
Chemistry
Hyponatremia	11	13
Hypomagnesemia	11	6
Hyperglycemia	5	5
Increased Alkaline Phosphatase	4.9	3.5
Increased ALT	4.9	2.7
Increased AST	4.6	1.2
Hypocalcemia	3.5	2.4
Blood creatinine increased	3.4	1.1
Hyperkalemia	1.5	3.1
TSH decreased < LLN§ and ≥ LLN at baseline	NA	NA
Hematology
Neutropenia	41	48
Lymphopenia	14	13
Anemia	13	22
Thrombocytopenia	12	15

Biliary Tract Cancer

Locally Advanced or Metastatic BTC - TOPAZ-1

The safety of IMFINZI in combination with gemcitabine and cisplatin in locally advanced or metastatic BTC was evaluated in TOPAZ-1, a randomized, double-blind, placebo-controlled, multicenter study. A total of 338 patients received IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks up to 8 cycles followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. Patients with active or prior documented autoimmune or inflammatory disorders, HIV infection or other active infections, including tuberculosis or hepatitis C were ineligible [see Clinical Studies (14.3)].

IMFINZI was discontinued due to adverse reactions in 6% of the patients receiving IMFINZI plus chemotherapy. The most frequently reported events resulting in discontinuation were sepsis (3 patients) and ischemic stroke (2 patients). The remaining events were dispersed across system organ classes and reported in 1 patient each. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients) and upper gastrointestinal hemorrhage (2 patients). The most common adverse reactions (occurring in ≥ 20% of patients) were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash and pyrexia. Table 15 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy.

Table 15. Adverse Reactions Occurring in ≥ 10% of Patients in the TOPAZ-1 Study
* Graded according to NCI CTCAE version 5.0. † Includes fatigue, malaise, cancer fatigue and asthenia. ‡ Includes abdominal pain, abdominal pain lower, abdominal pain upper and flank pain. § Includes rash macular, rash maculopapular, rash morbilliform, rash papular, rash pruritic, rash pustular, rash erythematous, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, erythema, dermatitis and rash.
	IMFINZI with Gemcitabine and Cisplatin N = 338		Placebo with Gemcitabine and Cisplatin N = 342
Adverse Reaction	All Grades* (%)	Grade* 3-4 (%)	All Grades* (%)	Grade* 3-4 (%)
General disorders and administration site conditions
Fatigue†	42	6	43	6
Pyrexia	20	1.5	16	0.6
Gastrointestinal disorders
Nausea	40	1.5	34	1.8
Constipation	32	0.6	29	0.3
Abdominal pain‡	24	0.6	23	2.9
Vomiting	18	1.5	18	2.0
Diarrhea	17	1.2	15	1.8
Metabolism and nutrition disorders
Decreased appetite	26	2.1	23	0.9
Skin and subcutaneous tissue disorders
Rash§	23	0.9	14	0
Pruritus	11	0	8	0
Psychiatric disorders
Insomnia	10	0	11	0

Table 16 summarizes the laboratory abnormalities in patients treated with IMFINZI plus chemotherapy.

Table 16. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20%* of Patients in the TOPAZ-1 study
* The frequency cut off is based on any grade change from baseline. † Graded according to NCI CTCAE version 5.0. Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with gemcitabine/cisplatin (range: 312 to 335) and Placebo with gemcitabine/cisplatin (range: 319 to 341).
	IMFINZI with Gemcitabine and Cisplatin	Placebo with Gemcitabine and Cisplatin
Laboratory Abnormality	Grade† 3 or 4 (%)	Grade† 3 or 4 (%)
Chemistry
Hyponatremia	18	13
Gamma-glutamyltransferase increased	12	13
Increased bilirubin	10	14
Hypokalemia	8	4.4
Increased AST	8	8
Increased ALT	7	6
Blood creatinine increased	5	2.1
Hypomagnesemia	4.5	2.2
Hypoalbuminemia	3.6	2.9
Hyperkalemia	2.1	2.1
Increased Alkaline Phosphatase	1.8	3.8
Hypocalcemia	1.8	2.4
Hematology
Neutropenia	48	49
Anemia	31	28
Leukopenia	28	28
Lymphopenia	23	15
Thrombocytopenia	18	18

Hepatocellular Carcinoma

Unresectable HCC - HIMALAYA

The safety of IMFINZI in combination with tremelimumab-actl was evaluated in a total of 388 patients with uHCC in HIMALAYA, a randomized, open-label, multicenter study [see Clinical Studies (14.1)]. Patients received IMFINZI 1,500 mg administered as a single intravenous infusion in combination with tremelimumab-actl 300 mg on the same day, followed by IMFINZI every 4 weeks or sorafenib 400 mg given orally twice daily.

Serious adverse reactions occurred in 41% of patients who received IMFINZI in combination with tremelimumab-actl. Serious adverse reactions in > 1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI in combination with tremelimumab-actl, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). The most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients; the most common adverse reactions leading to treatment discontinuation (≥ 1%) were hemorrhage (1.8%), diarrhea (1.5%), AST increased (1%), and hepatitis (1%).

Dosage interruptions or delay of the treatment regimen due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption or delay in ≥ 1% of patients included ALT increased (3.6%), diarrhea (3.6%), rash (3.6%), amylase increased (3.4%), AST increased (3.1%), lipase increased (2.8%), pneumonia (1.5%), hepatitis (1.5%), pyrexia (1.5%), anemia (1.3%), thrombocytopenia (1%), hyperthyroidism (1%), pneumonitis (1%), and blood creatinine increased (1%).

Table 17 summarizes the adverse reactions that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study.

Table 17. Adverse Reactions Occurring in ≥ 10% of Patients in the HIMALAYA Study
	IMFINZI and Tremelimumab-actl (N = 388)		Sorafenib (N = 374)
Adverse Reaction	All Grades (%)	Grade 3-4 (%)	All Grades (%)	Grade 3-4 (%)
* Represents a composite of multiple related terms.
Skin and subcutaneous tissue disorders
Rash*	32	2.8	57	12
Pruritus	23	0	6	0.3
Gastrointestinal disorders
Diarrhea*	27	6	45	4.3
Abdominal pain*	20	1.8	24	4
Nausea	12	0	14	0
General disorders and administration site conditions
Fatigue*	26	3.9	30	6
Pyrexia	13	0.3	9	0.3
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain*	22	2.6	17	0.8
Metabolism and nutrition disorders
Decreased appetite	17	1.3	18	0.8
Endocrine disorders
Hypothyroidism*	14	0	6	0
Psychiatric disorders
Insomnia	10	0.3	4.3	0

Table 18 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study.

Table 18. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the HIMALAYA study
* Graded according to NCI CTCAE version 4.03. † Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with tremelimumab-actl (range: 367-378) and sorafenib (range:344-352).
	IMFINZI and Tremelimumab-actl		Sorafenib
Laboratory Abnormality	Any grade* (%)†	Grade 3* or 4 (%)†	Any grade*(%)†	Grade 3* or 4 (%)†
Chemistry
Aspartate Aminotransferase increased	63	27	55	21
Alanine Aminotransferase increased	56	18	53	12
Sodium decreased	46	15	40	11
Bilirubin increased	41	8	47	11
Alkaline Phosphatase increased	41	8	44	5
Glucose increased	39	14	29	4
Calcium decreased	34	0	43	0.3
Albumin decreased	31	0.5	37	1.7
Potassium increased	28	3.8	21	2.6
Creatinine increased	21	1.3	15	0.9
Hematology
Hemoglobin decreased	52	4.8	40	6
Lymphocytes decreased	41	11	39	10
Platelets decreased	29	1.6	35	3.1
Leukocytes decreased	20	0.8	30	1.1

Endometrial Cancer

Advanced or Recurrent dMMR Endometrial Cancer – DUO-E

The safety of IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent was evaluated in 44 patients with dMMR advanced or recurrent endometrial cancer in DUO-E, a randomized, double-blind, placebo-controlled trial [See Clinical Studies (14.5)]. Patients received IMFINZI 1,120 mg with carboplatin and paclitaxel every 3 weeks for up to six 21-day cycles followed by IMFINZI 1,500 mg every 4 weeks or carboplatin and paclitaxel every 3 weeks for up to six 21-day cycles alone. Treatment was continued until disease progression or unacceptable toxicity. The median duration of exposure to IMFINZI with carboplatin and paclitaxel was 14.8 months (range: 0.7 to 31.7).

Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel. The most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).

Permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. The adverse reaction which resulted in permanent discontinuation of IMFINZI (≥4%) was rash (4.5%).

Dosage interruptions of IMFINZI due to adverse reactions occurred in 52% of patients. Adverse reactions which required dosage interruptions of IMFINZI (≥4%) were anemia (11%), thrombocytopenia (9%), neutropenia (9%), COVID-19 (9%), increased ALT (4.5%), and pneumonitis (4.5%).

The most common adverse reactions (>20%), including laboratory abnormalities, were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, increased alkaline phosphatase, and decreased appetite.

Tables 19 and 20 summarize adverse reactions and laboratory abnormalities in DUO-E, respectively.

Table 19. Adverse Reactions Occurring in ≥ 10% of Patients with dMMR tumors in DUO-E
* Includes neuropathy peripheral, peripheral sensory neuropathy, hypoasthesia, peripheral motor neuropathy, and parasthesia. † Includes arthralgia, pain in extremity, back pain, non-cardiac chest pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, arthritis, bone pain, musculoskeletal stiffness, neck pain, musculoskeletal discomfort, and spinal pain. ‡ Includes abdominal pain, abdominal pain lower, flank pain, abdominal discomfort, and abdominal pain upper. § Includes constipation and fecaloma. ¶ Includes eczema, rash, rash erythematous, rash maculo-papular, dermatitis, rash pustular, skin exfoliation, and symmetrical drug-related intertriginous, and flexural exanthema. # Includes asthenia and fatigue. Þ Includes peripheral edema, peripheral swelling, and edema. ß Includes dyspnea and exertional dyspnea. à Includes nasopharyngitis, pharyngitis, rhinitis, sinusitis, tracheobronchitis, and upper respiratory tract infection. è Includes blood thyroid stimulating hormone increased, and hypothyroidism.
Adverse Reactions	IMFINZI with Carboplatin and Paclitaxel (N=44)		Carboplatin and Paclitaxel (N=46)
Adverse Reactions	All Grades (%)	Grade 3-4 (%)	All Grades (%)	Grade 3-4 (%)
Nervous system disorders
Peripheral neuropathy*	61	2.3	61	4.3
Headache	23	0	17	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain†	59	2.3	52	2.2
Gastrointestinal disorders
Nausea	59	0	48	2.2
Abdominal pain‡	39	0	24	2.2
Constipation§	39	4.5	35	2.2
Diarrhea	27	2.3	24	2.2
Vomiting	27	0	22	4.3
Skin and subcutaneous tissue disorders
Alopecia	52	0	41	0
Rash¶	39	2.3	17	2.2
Pruritus	16	0	11	0
General disorders and administration site conditions
Fatigue#	41	4.5	57	11
Peripheral edemaÞ	16	0	13	2.2
Respiratory, thoracic and mediastinal disorders
Cough / productive cough	27	0	20	0
Dyspneaß	25	2.3	9	0
Metabolism and nutrition disorders
Decreased appetite	18	0	18	0
Infections and infestations
Upper respiratory tract infectionà	14	0	4.3	0
Endocrine disorders
Hypothyroidismè	11	0	4.3	0

Clinically relevant adverse reactions in <10% of patients who received IMFINZI with carboplatin and paclitaxel included autoimmune hemolytic anemia, colitis, immune-mediated thyroiditis, infusion related reaction, interstitial lung disease, myositis, pneumonitis, pulmonary embolism, and sepsis.

Table 20 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI with carboplatin and paclitaxel followed by IMFINZI as a single agent.

Table 20. Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients with dMMR tumors in DUO-E
Laboratory Abnormality	IMFINZI with Carboplatin and Paclitaxel*		Carboplatin and Paclitaxel ‡
Laboratory Abnormality	All Grades (%)	Grade 3-4 (%)	All Grades (%)		Grade 3-4 (%)
* Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI with carboplatin and paclitaxel (range: 40 to 44), and carboplatin and paclitaxel (range: 37 to 46)
Chemistry
Magnesium decreased	36	0	30	2.5
ALT increased	32	2.3	22	2.2
AST increased	30	2.3	22	0
Potassium decreased	25	0	24	2.2
Alkaline phosphatase increased	20	0	16	0