Imfinzi Adverse Reactions

The safety of IMFINZI as monotherapy is based on pooled data in 3006 patients from 9 studies across multiple tumor types. The most frequent adverse reaction were cough (21.5%), diarrhoea (16.3%) and rash (16.0%). Adverse drug reactions are listed according to system organ class in MedDRA. Within each system organ class, the adverse drug reactions are presented in decreasing frequency. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. The corresponding frequency category for each ADR is defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from available data).
Infections and infestations: Very common: Upper respiratory tract infections^o (13.5%) (CTCAE grade 3 and above: uncommon [0.2%]).
Common: Pneumonia^a,p (8.9%) (CTCAE grade 3 and above: common [3.5%]), Dental and oral soft tissue infections^q (1.7%) (CTCAE grade 3 and above: rare [<0.1%]), Oral candidiasis (2.1%) (CTCAE grade 3 and above: very rare [0%]), Influenza (1.6%) (CTCAE grade 3 and above: rare [<0.1%]).
Endocrine disorders: Very common: Hypothyroidism^g (10.1%) (CTCAE grade 3 and above: uncommon [0.2%]).
Common: Hyperthyroidism^h (4.6%) (CTCAE grade 3 and above: very rare [0%]).
Uncommon: Adrenal insufficiency (0.6%) (CTCAE grade 3 and above: rare [<0.1%]), Thyroiditisⁱ (0.8%) (CTCAE grade 3 and above: rare [<0.1%]).
Rare: Type 1 diabetes mellitus (<0.1%) (CTCAE grade 3 and above: rare [<0.1%]), Hypophysitis/Hypopituitarism (<0.1%) (CTCAE grade 3 and above: rare [<0.1%]), Diabetes insipidus (<0.1%) (CTCAE grade 3 and above: [<0.1%]).
Cardiac disorders: Rare: Myocarditis (<0.1%) (CTCAE grade 3 and above: rare [<0.1%]).
Respiratory, thoracic and mediastinal disorders: Very common: Cough/Productive cough^a (21.5%) (CTCAE grade 3 and above: uncommon [0.4%]).
Common: Pneumonitis^a (3.8%) (CTCAE grade 3 and above: uncommon [0.9%]), Dysphonia (3.1%) (CTCAE grade 3 and above: rare [<0.1%]).
Uncommon: Interstitial lung disease (0.6%) (CTCAE grade 3 and above: uncommon [<0.1%]).
Gastrointestinal disorders: Very common: Diarrhoea (16.3%) (CTCAE grade 3 and above: uncommon [0.6%]), Abdominal pain^d (12.7%) (CTCAE grade 3 and above: common [1.8%]).
Uncommon: Colitis^e (0.9%), (CTCAE grade 3 and above: uncommon [0.3%]), Pancreatitis^f (0.23%) (CTCAE grade 3 and above: uncommon [0.17%]).
Hepatobiliary disorders: Common: Aspartate aminotransferase increased or Alanine aminotransferase increased^a,b (8.1%) (CTCAE grade 3 and above: common [2.3%]).
Uncommon: Hepatitis^a,c (0.8%) (CTCAE grade 3 and above: uncommon [0.4%]).
Skin and subcutaneous tissue disorders: Very common: Rash^k (16%) (CTCAE grade 3 and above: uncommon [0.6%]), Pruritus^l (10.8%) (CTCAE grade 3 and above: rare [<0.1%]).
Common: Night sweats (1.6%) (CTCAE grade 3 and above: rare [<0.1%]).
Uncommon: Dermatitis (0.7%) (CTCAE grade 3 and above: rare [<0.1%]).
Rare: Pemphigoid^m (0.1%) (CTCAE grade 3 and above: very rare [0%]).
Musculoskeletal and connective tissue disorders: Common: Myalgia (5.9%) (CTCAE grade 3 and above: rare [<0.1%]).
Uncommon: Myositis (0.2%) (CTCAE grade 3 and above: rare [<0.1%]).
Very rare: Polymyositis (Not determined^r ) (frequency of CTCAE grade 3 and above: very rare [Not determined^r ]).
Renal and urinary disorders: Common: Blood creatinine increased (3.5%) (CTCAE grade 3 and above: rare [<0.1%]), Dysuria (1.3%) (CTCAE grade 3 and above: very rare [0%]).
Uncommon: Nephritis^j (0.3%) (CTCAE grade 3 and above: rare [<0.1%]).
General disorders and administration site conditions: Very common: Pyrexia (13.8%) (CTCAE grade 3 and above: uncommon [0.3%]).
Common: Oedema peripheralⁿ (9.7%) (CTCAE grade 3 and above: uncommon [0.3%]).
Nervous system disorders: Not known: Myasthenia gravis (Not determined^s) (CTCAE grade 3 and above: uncommon [Not determined^s]), Encephalitis (Not determined^t) (CTCAE grade 3 and above: [Not determined^t].
Blood and lymphatic system disorders: Rare: Immune thrombocytopenia^a (<0.1%) (CTCAE grade 3 and above: rare [<0.1%]).
Injury, poisoning and procedural complications: Infusion-related reaction^u (1.6%) (CTCAE grade 3 and above: uncommon [0.2%]).
^a Including fatal outcome.
^b Includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased.
^c Includes hepatitis, autoimmune hepatitis, hepatitis toxic, hepatocellular injury, hepatitis acute, hepatotoxicity, and immune-mediated hepatitis.
^d Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain.
^e Includes colitis, enteritis, enterocolitis, and proctitis.
^f Includes pancreatitis and pancreatitis acute.
^g Includes autoimmune hypothyroidism and hypothyroidism.
^h Includes hyperthyroidism and Basedow's disease.
ⁱ Includes autoimmune thyroiditis, thyroiditis, and thyroiditis subacute.
^j Includes autoimmune nephritis, tubulointerstitial nephritis, nephritis, glomerulonephritis, and glomerulonephritis membranous.
^k Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, and rash.
^l Includes pruritus generalized and pruritus.
^m Includes pemphigoid, dermatitis bullous, and pemphigus. Reported frequency from completed and ongoing trials is uncommon.
ⁿ Includes oedema peripheral and peripheral swelling.
^o Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection.
^p Includes lung infection, Pneumocystis jirovecii pneumonia, pneumonia, candida pneumonia, pneumonia legionella, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia pneumococcal, and pneumonia streptococcal.
^q Includes gingivitis, oral infection, periodontitis, pulpitis dental, tooth abscess, and tooth infection.
^r Polymyositis (fatal) was observed in a patient treated with IMFINZI from an ongoing sponsored clinical study outside of the pooled dataset: rare in any grade, rare in Grade 3 or 4 or 5.
^s Reported frequency from AstraZeneca-sponsored clinical studies outside of the pooled dataset is rare, with no events at Grade >2.
^t Reported frequency from ongoing AstraZeneca-sponsored clinical studies outside of the pooled dataset is rare and includes two events of encephalitis, one was Grade 5 (fatal) and one was Grade 2.
^u Includes infusion-related reaction and urticaria with onset on the day of dosing or 1 day after dosing.
The safety of IMFINZI in combination with chemotherapy is based on data in 265 patients from the CASPIAN (SCLC) study and was consistent with IMFINZI monotherapy and known chemotherapy safety profile.
The safety of IMFINZI in combination with chemotherapy is based on data in 338 patients from the TOPAZ-1 (BTC) study and was consistent with IMFINZI monotherapy and known chemotherapy safety profiles.
The safety of IMFINZI in combination with tremelimumab and platinum-based chemotherapy is based on data in 330 patients from the POSEIDON (metastatic NSCLC) study and was consistent with known IMFINZI + tremelimumab and known chemotherapy safety profiles.
The safety of STRIDE is based on data in 462 patients from the HCC pool (uHCC) and was consistent with known IMFINZI + tremelimumab safety profile.
Description of selected adverse reactions: The data as follows reflect information for significant adverse reactions for IMFINZI as monotherapy in the pooled safety dataset across tumor types (n=3006). IMFINZI in combination with tremelimumab (75 mg Q4W; pan-tumour pool) in the pooled safety dataset across tumour types (n=2280) and STRIDE in the HCC pool (n=462).
The management guidelines for these adverse reactions are described in Dosage & Administration and Precautions.
Immune-mediated pneumonitis: In patients receiving IMFINZI monotherapy, immune-mediated pneumonitis occurred in 92 (3.1%) patients, including Grade 3 in 25 (0.8%) patients, Grade 4 in 2 (<0.1%) patients, and Grade 5 in 6 (0.2%) patients. The median time to onset was 55 days (range: 2-785 days). Sixty-nine of the 92 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day), 2 patients also received infliximab and 1 patient also received cyclosporine. IMFINZI was discontinued in 38 patients. Resolution occurred in 53 patients. Immune-mediated pneumonitis occurred more frequently in patients in the PACIFIC Study who had completed treatment with concurrent chemoradiation within 1 to 42 days prior to initiation of the study (9.9%), compared to the other patients in the combined safety database (1.8%).
In the PACIFIC Study, in patients with locally advanced, unresectable NSCLC (n=475 in the IMFINZI arm, and n=234 in the placebo arm) who had completed treatment with concurrent chemoradiation within 1 to 42 days prior to initiation of the study, immune-mediated pneumonitis occurred in 47 (9.9%) patients in the IMFINZI-treated group and 14 (6.0%) patients in the placebo group, including Grade 3 in 9 (1.9%) patients on IMFINZI vs. 6 (2.6%) patients on placebo and Grade 5 in 4 (0.8%) patients on IMFINZI vs. 3 (1.3%) patients on placebo. The median time to onset in the IMFINZI-treated group was 46 days (range: 2-342 days) vs. 57 days (range: 26-253 days) in the placebo group. In the IMFINZI-treated group, 30 patients who received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day), and 2 patients also received infliximab. In the placebo group 12 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and 1 patient also received cyclophosphamide and tacrolimus. Resolution occurred for 29 patients in the IMFINZI treated group vs 6 in placebo.
Radiation pneumonitis is frequently observed in patients receiving radiation therapy to the lung and the clinical presentation of pneumonitis and radiation pneumonitis is very similar. In the PACIFIC study, pneumonitis including both immune-mediated pneumonitis and radiation pneumonitis, occurred in 161 (33.9%) patients in the IMFINZI-treated group and 58 (24.8%) in the placebo group including grade 3 (3.4% vs. 3.0% respectively) and grade 5 (1.1 vs. 1.7%).
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated pneumonitis occurred in 86 (3.8%) patients, including Grade 3 in 30 (1.3%) patients, Grade 4 in 1 (<0.1%) patient, and Grade 5 in 7 (0.3%) patients. The median time to onset was 57 days (range: 8-912 days). All patients received systemic corticosteroids, and 79 of the 86 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seven patients also received other immunosuppressants. Treatment was discontinued in 39 patients. Resolution occurred in 51 patients.
HCC pool: In patients receiving STRIDE, immune--mediated pneumonitis occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient and Grade 5 (fatal) in 1 (0.2%) patient. The median time to onset was 29 days (range: 5-774 days). Six patients received systemic corticosteroids, and 5 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient also received other immunosuppressants. Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated hepatitis: In patients receiving IMFINZI monotherapy, immune-mediated hepatitis occurred in 67 (2.2%) patients, including Grade 3 in 35 (1.2%) patients, Grade 4 in 6 (0.2%) and Grade 5 in 4 (0.1%) patients. The median time to onset was 36 days (range: 3-333 days). Forty-four of the 67 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also received mycophenolate treatment. IMFINZI was discontinued in 9 patients. Resolution occurred in 29 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated hepatitis occurred in 80 (3.5%) patients, including Grade 3 in 48 (2.1%) patients, Grade 4 in 8 (0.4%) patients, and Grade 5 in 2 (<0.1%) patients. The median time to onset was 36 days (range: 1-533 days). All patients received systemic corticosteroids, and 68 of the 80 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Eight patients also received other immunosuppresants. Treatment was discontinued in 27 patients. Resolution occurred in 47 patients.
HCC pool: In patients receiving STRIDE, immune-mediated hepatitis occurred in 34 (7.4%) patients, including Grade 3 in 20 (4.3%) patients, Grade 4 in 1 (0.2%) patient and Grade 5 (fatal) in 3 (0.6%) patients. The median time to onset was 29 days (range: 13-313 days). All patients received systemic corticosteroids, and 32 of the 34 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Nine patients also received other immunosuppressants. Treatment was discontinued in 10 patients. Resolution occurred in 13 patients.
Immune-mediated colitis: IMFINZI monotherapy, immune-mediated colitis or diarrhea occurred in 58 (1.9%) patients, including Grade 3 in 9 (0.3%) patients and Grade 4 in 2 (<0.1%) patient. The median time to onset was 70 days (range: 1-394 days). Thirty-eight of the 58 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient also received infliximab treatment and one patient also received mycophenolate treatment. IMFINZI was discontinued in 9 patients. Resolution occurred in 43 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated colitis or diarrhoea occurred in 167 (7.3%) patients, including Grade 3 in 76 (3.3%) patients and Grade 4 in 3 (0.1%) patients. The median time to onset was 57 days (range: 3-906 days). All patients received systemic corticosteroids, and 151 of the 167 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty-two patients also received other immunosuppressants. Treatment was discontinued in 54 patients. Resolution occurred in 141 patients.
Intestinal perforation was observed in patients receiving IMFINZI in combination with tremelimumab.
HCC pool: In patients receiving STRIDE, immune-mediated colitis or diarrhoea occurred in 31 (6.7%) patients, including Grade 3 in 17 (3.7%) patients. The median time to onset was 23 days (range: 2-479 days). All patients received systemic corticosteroids, and 28 of the 31 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also received other immunosuppressants. Treatment was discontinued in 5 patients. Resolution occurred in 29 patients.
Intestinal perforation was not observed in patients receiving STRIDE.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism: In patients receiving IMFINZI monotherapy, immune-mediated hypothyroidism occurred in 245 (8.2%) patients, including Grade 3 in 4 (0.1%) patients. The median time to onset was 85 days (range: 1-562 days). Of the 245 patients, 240 patients received hormone replacement therapy, 6 patients received high-dose corticosteroids (at least 40 mg prednisone or equivalent per day) for immune-mediated hypothyroidism followed by hormone replacement. No patients discontinued IMFINZI due to immune-mediated hypothyroidism. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 20 patients or immune-mediated thyroiditis in 3 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated hypothyroidism occurred in 209 (9.2%) patients, including Grade 3 in 6 (0.3%) patients. The median time to onset was 85 days (range: 1-624 days). Thirteen patients received systemic corticosteroids, and 8 of the 13 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Two-hundred and five patients required endocrine therapy. Treatment was discontinued in 3 patients. Resolution occurred in 52 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 25 patients or immune-mediated thyroiditis in 2 patients.
HCC pool: In patients receiving STRIDE, immune-mediated hypothyroidism occurred in 46 (10.0%) patients. The median time to onset was 85 days (range: 26-763 days). One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker).
Resolution occurred in 6 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 4 patients.
Immune-mediated hyperthyroidism: In patients receiving IMFINZI monotherapy, immune-mediated hyperthyroidism occurred in 50 (1.7%) patients, there were no Grade 3 or 4 cases. The median time to onset was 43 days (range: 1-253 days). Forty-six of the 50 patients received medical therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker or beta-blocker), 11 patients received systemic corticosteroids and 4 of the 11 patients received high-dose systemic corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient discontinued IMFINZI due to immune-mediated hyperthyroidism. Resolution occurred in 39 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated hyperthyroidism occurred in 62 (2.7%) patients, including Grade 3 in 5 (0.2%) patients. The median time to onset was 33 days (range: 4-176 days). Eighteen patients received systemic corticosteroids, and 11 of the 18 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Fifty-three patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or betablocker). Treatment was discontinued in 1 patient. Resolution occurred in 47 patients.
HCC pool: In patients receiving STRIDE, immune-mediated hyperthyroidism occurred in 21 (4.5%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 30 days (range: 13-60 days). Four patients received systemic coticosteriods, and all of the four patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). One patient discontinued treatment due to hyperthyroidism. Resolution occurred in 17 patients.
Immune-mediated thyroiditis: In patients receiving IMFINZI monotherapy, immune-mediated thyroiditis occurred in 12 (0.4%) patients, including Grade 3 in 2 ( <0.1%) patients. The median time to onset was 49 days (range: 14-106 days). Of the 12 patients, 10 patients received hormone replacement therapy, 1 patient received high-dose corticosteroids (at least 40 mg prednisone or equivalent per day). One patient discontinued IMFINZI due to immune-mediated thyroiditis.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated thyroiditis occurred in 15 (0.7%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 57 days (range: 22-141 days). Five patients received systemic corticosteroids, and 2 of the 5 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Thirteen patients required other therapy, including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. No patients discontinued treatment due to immune-mediated thyroiditis. Resolution occurred in 5 patients.
HCC pool: In patients receiving STRIDE, immune-mediated thyroiditis occurred in 6 (1.3%) patients. The median time to onset was 56 days (range: 7-84 days). Two patients received systemic corticosteroids, and 1 of the 2 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. Resolution occurred in 2 patients.
Immune-mediated adrenal insufficiency: In patients receiving IMFINZI monotherapy, immune-mediated adrenal insufficiency occurred in 14 (0.5%) patients, including Grade 3 in 3 (<0.1%) patients. The median time to onset was 146 days (range: 20-547 days). All 14 patients received systemic corticosteroids; 4 of the 14 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). No patients discontinued IMFINZI due to Immune-mediated adrenal insufficiency. Resolution occurred in 3 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated adrenal insufficiency occurred in 33 (1.4%) patients, including Grade 3 in 16 (0.7%) patients and Grade 4 in 1 (<0.1%) patient. The median time to onset was 105 days (range: 20-428 days). Thirty-two patients received systemic corticosteroids, and 10 of the 32 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seven patients required endocrine therapy. Treatment was discontinued in 1 patient. Resolution occurred in 11 patients.
HCC pool: In patients receiving STRIDE, immune-mediated adrenal insufficiency occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 64 days (range: 43-504 days). All patients received systemic corticosteroids, and 1 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Resolution occurred in 2 patients.
Immune-mediated type 1 diabetes mellitus: In patients receiving IMFINZI monotherapy, Grade 3 immune-mediated type 1 diabetes mellitus occurred in 1 (<0.1%) patient. The time to onset was 43 days. This patient required long-term insulin therapy and IMFINZI was permanently discontinued due to immune-mediated type 1 diabetes mellitus.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated type 1 diabetes occurred in 6 (0.3%) patients, including Grade 3 in 1 (<0.1%) patient and Grade 4 in 2 (<0.1%) patients. The median time to onset was 58 days (range: 7-220 days). All patients required insulin. Treatment was discontinued in 1 patient. Resolution occurred in 1 patient.
HCC pool: In patients receiving STRIDE, immune-mediated type 1 diabetes mellitus was not observed.
Immune-mediated hypophysitis/hypopituitarism: In patients receiving IMFINZI monotherapy, immune-mediated hypophysitis/hypopituitarism occurred in 2 (<0.1%) patients (both Grade 3). The time to onset for the events was 44 days and 50 days. Both patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and one patient discontinued IMFINZI due to immune-mediated hypophysitis/hypopituitarism.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated hypophysitis/hypopituitarism occurred in 16 (0.7%) patients, including Grade 3 in 8 (0.4%) patients. The median time to onset was 123 days (range: 63-388 days). All patients received systemic corticosteroids, and 8 of the 16 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also required endocrine therapy. Treatment was discontinued in 2 patients. Resolution occurred in 7 patients.
HCC pool: In patients receiving STRIDE, immune-mediated hypophysitis/hypopituitarism occurred in 5 (1.1%) patients. The median time to onset for the events was 149 days (range: 27-242 days). Four patients received systemic corticosteroids, and 1 of the 4 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also required endocrine therapy. Resolution occurred in 2 patients.
Immune-mediated nephritis: In patients receiving IMFINZI monotherapy, immune-mediated nephritis occurred in 14 (0.5%) patients, including Grade 3 in 2 (<0.1%) patients. The median time to onset was 71 days (range: 4-393 days). Nine patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and 1 patient also received mycophenolate. IMFINZI was discontinued in 5 patients. Resolution occurred in 8 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated nephritis occurred in 9 (0.4%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 79 days (range: 39-183 days). All patients received systemic corticosteroids, and 7 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 3 patients. Resolution occurred in 5 patients.
HCC pool: In patients receiving STRIDE, immune-mediated nephritis occurred in 4 (0.9%) patients, including Grade 3 in 2 (0.4%) patients. The median time to onset was 53 days (range: 26-242 days). All patients received systemic corticosteroids, and 3 of the 4 received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated rash: In patients receiving IMFINZI monotherapy, immune-mediated rash or dermatitis (including pemphigoid) occurred in 50 (1.7%) patients, including Grade 3 in 12 (0.4%) patients. The median time to onset was 43 days (range: 4-333 days). Twenty-four of the 50 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI was discontinued in 3 patients. Resolution occurred in 31 patients.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, immune-mediated rash or dermatitis (including pemphigoid), occurred in 112 (4.9%) patients, including Grade 3 in 17 (0.7%) patients. The median time to onset was 35 days (range: 1-778 days). All patients received systemic corticosteroids, and 57 of the 112 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 10 patients. Resolution occurred in 65 patients.
HCC pool: In patients receiving STRIDE, immune-mediated rash or dermatitis (including pemphigoid) occurred in 26 (5.6%) patients, including Grade 3 in 9 (1.9%) patients and Grade 4 in 1 (0.2%) patients. The median time to onset was 25 days (range: 2-933 days). All patients received systemic corticosteroids and 14 of the 26 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient received other immunosuppressants. Treatment was discontinued in 3 patients. Resolution occurred in 19 patients.
Infusion-related reactions: In patients receiving IMFINZI monotherapy, infusion-related reactions occurred in 49 (1.6%) patients, including Grade 3 in 5 (0.2%) patients. There were no Grade 4 or 5 events.
IMFINZI + tremelimumab pan-tumour pool: In patients receiving IMFINZI in combination with tremelimumab, infusion-related reactions occurred in 45 patients (2.0%), including Grade 3 in 2 (<0.1%) patients. There were no Grade 4 or 5 events.
HCC pool: In patients receiving STRIDE, infusion-related reactions occurred in 13 (2.8%) patients.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. Immunogenicity of IMFINZI as monotherapy is based on pooled data in 2280 patients who were treated with IMFINZI 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as a single-agent and evaluable for the presence of anti-drug antibodies (ADA). Sixty-nine patients (3.0%) tested positive for treatment-emergent ADA. Neutralising antibodies against durvalumab were detected in 0.5% (12/2280) of patients. The presence of ADAs did not have a clinically relevant effect on pharmacokinetics, pharmacodynamics or safety.
In the CASPIAN study, of the 201 patients who were treated with IMFINZI 1500 mg every 3 weeks in combination with chemotherapy and evaluable for the presence of ADAs, 0 (0%) patients tested positive for treatment-emergent ADAs. The types of AEs reported in patients positive for durvalumab ADA were similar to those reported in patients who were negative for durvalumab ADA. The impact of treatment-emergent ADA on pharmacokinetics and clinical safety of durvalumab was not evaluable as no patient samples tested positive for treatment-emergent durvalumab ADA.
In the TOPAZ-1 study, of the 240 patients who were treated with IMFINZI 1500 mg every 3 weeks in combination with chemotherapy, followed by IMFINZI 1500 mg every 4 weeks and evaluable for the presence of ADAs, 2 (0.8%) patients tested positive for treatment-emergent ADAs. There were insufficient numbers of patients with treatment emergent ADAs or neutralizing antibodies (2 patients each) to determine whether ADAs have an impact on pharmacokinetics and clinical safety of durvalumab.
In the POSEIDON study, of the 286 patients who were treated with IMFINZI 1500 mg in combination with tremelimumab every 3 weeks and platinum-based chemotherapy and evaluable for the presence of ADAs, 29 (10.1%) patients tested positive for treatment-emergent ADAs. Neutralizing antibodies against durvalumab were detected in 1% (3/286) patients. The presence of ADAs did not have an apparent effect on pharmacokinetics or safety.
In the HIMALAYA study, of the 294 patients who were treated with STRIDE and evaluable for the presence of ADAs, 9 (3.1%) patients tested positive for treatment-emergent ADAs. Neutralizing antibodies against durvalumab were detected in 1.7% (5/294) patients. The presence of ADAs did not have an apparent effect on pharmacokinetics or safety.
Immunogenicity assay results are highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease.
For these reasons, comparison of incidence of antibodies to IMFINZI with the incidence of antibodies to other products may be misleading.