Jemperli Adverse Reactions

Summary of the safety profile: Dostarlimab is most commonly associated with immune-related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of dostarlimab (see Description of selected adverse reactions as follows).
Dostarlimab in monotherapy: The safety of dostarlimab has been evaluated in 605 patients with EC or other advanced solid tumours who received dostarlimab monotherapy in the GARNET study, including 153 patients with advanced or recurrent dMMR/MSI-H EC. Patients received doses of 500 mg every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks for all cycles thereafter.
In patients with advanced or recurrent solid tumours (N = 605), the most common adverse reactions (>10%) were anaemia (28.6%), diarrhoea (26.0%), nausea (25.8%), vomiting (19.0%), arthralgia (17.0%), pruritus (14.2%), rash (13.2%), pyrexia (12.4%), aspartate aminotransferase increased (11.2%) and hypothyroidism (11.2%). JEMPERLI was permanently discontinued due to adverse reactions in 38 (6.3%) patients; most of them were immune-related events. Adverse reactions were serious in 11.2% of patients; most serious adverse reactions were immune-related adverse reactions (see Precautions).
The safety profile for patients with dMMR/MSI-H EC in the GARNET study (N = 153) was not different from that of the overall monotherapy population presented in Table 6.
Dostarlimab in combination with chemotherapy: The safety of dostarlimab has been evaluated in 241 patients with primary advanced or recurrent EC who received dostarlimab in combination with paclitaxel and carboplatin in the RUBY study. Patients received doses of 500 mg dostarlimab every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for all cycles thereafter.
In patients with primary advanced or recurrent EC (N = 241), the most common adverse reactions (≥10%) were rash (23.2%), rash maculopapular (14.5%), hypothyroidism (14.5%), pyrexia (12.9%), alanine aminotransferase increased (12.9 %), aspartate aminotransferase increased (12.0 %) and dry skin (10.0%). JEMPERLI was permanently discontinued due to adverse reactions in 12 (5.0%) patients; most were immune-related events. Adverse reactions were serious in 5.8% of patients; approximately one-half of serious adverse reactions were immune-related adverse reactions (see Precautions).
Tabulated list of adverse reactions: Adverse reactions reported in clinical trials of dostarlimab as a monotherapy or in combination with chemotherapy are listed in Table 6 by system organ class and by frequency. The frequencies of adverse reactions listed in the dostarlimab monotherapy column are based on all-cause adverse event frequency identified in 605 patients with advanced or recurrent solid tumours from the GARNET study exposed to dostarlimab monotherapy for a median duration of treatment of 24 weeks (range: 1 week to 229 weeks). Unless otherwise stated, the frequencies of adverse reactions listed in the dostarlimab in combination with chemotherapy column are based on all-cause adverse event frequency identified in 241 patients with primary advanced or recurrent EC from the RUBY study exposed to dostarlimab in combination with chemotherapy for a median duration of treatment of 43 weeks (range: 3.0 to 192.6 weeks). For additional safety information when dostarlimab is administered in combination, refer to the respective Prescribing Information for the combination products.
Adverse reactions known to occur with dostarlimab as monotherapy or combination therapy components given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical studies with combination therapy. These reactions are presented by system organ class and by frequency. Frequencies are 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); and not known (cannot be estimated from the available data). (See Table 6.)

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Description of selected adverse reactions: The selected adverse reactions described as follows are based on the safety of dostarlimab in a combined monotherapy safety database of 605 patients in the GARNET study in patients with EC or other advanced solid tumours. Immune-related adverse reactions were defined as events of grade 2 and above; the following frequencies exclude grade 1 events. Details for immune-related adverse reactions for dostarlimab when given in combination are presented if clinically relevant differences were noted in comparison to dostarlimab monotherapy. The management guidelines for these adverse reactions are described in Dosage & Administration.
Immune-related adverse reactions (see Precautions): Immune-related pneumonitis: Immune-related pneumonitis occurred in 14 (2.3%) patients, including grade 2 (1.3%), grade 3 (0.8%) and grade 4 (0.2%) pneumonitis. Pneumonitis led to discontinuation of dostarlimab in 8 (1.3%) patients.
Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 11 (78.6%) patients experiencing pneumonitis. Pneumonitis resolved in 11 (78.6%) patients.
Immune-related colitis: Colitis occurred in 8 (1.3%) patients, including grade 2 (0.7%) and grade 3 (0.7%) colitis. Colitis did not lead to discontinuation of dostarlimab in any patients.
Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 5 (62.5%) patients. Colitis resolved in 5 (62.5%) patients experiencing colitis.
Immune-related hepatitis: Hepatitis occurred in 3 (0.5%) patients, all of which were grade 3. Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 2 (66.7%) patients. Hepatitis led to discontinuation of dostarlimab in 1 (0.2%) patient and resolved in 2 of the 3 patients.
Immune-mediated endocrinopathies: Hypothyroidism occurred in 46 (7.6%) patients, all of which were grade 2. Hypothyroidism did not lead to discontinuation of dostarlimab and resolved in 17 (37.0%) patients.
Hypothyroidism occurred in 30 (12.4%) patients who received dostarlimab in combination with carboplatin-paclitaxel, all of which were grade 2. Hypothyroidism led to discontinuation of dostarlimab in 1 (0.4%) patient and resolved in 7 (23.3%) patients experiencing hypothyroidism.
Hyperthyroidism occurred in 14 (2.3%) patients, including grade 2 (2.1%) and grade 3 (0.2%). Hyperthyroidism did not lead to discontinuation of dostarlimab and resolved in 10 (71.4%) patients.
Hyperthyroidism occurred in 8 (3.3%) patients who received dostarlimab in combination with carboplatin-paclitaxel, including grade 2 (2.9%) and grade 3 (0.4%). Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 1 (12.5%) patient experiencing hyperthyroidism. Hyperthyroidism did not lead to discontinuation of dostarlimab and resolved in 6 (75%) patients experiencing hyperthyroidism.
Thyroiditis occurred in 3 (0.5%) patients; all were Grade 2. None of the events of thyroiditis resolved; there were no discontinuations of dostarlimab due to thyroiditis.
Adrenal insufficiency occurred in 7 (1.2%) patients, including grade 2 (0.5%), and grade 3 (0.7%). Adrenal insufficiency resulted in discontinuation of dostarlimab in 1 (0.2%) patient and resolved in 4 (57.1%) patients.
Immune-mediated nephritis: Nephritis, including tubulointerstitial nephritis, occurred in 3 (0.5%) patients; all were grade 2. Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 2 (66.7%) patients experiencing nephritis. Nephritis led to discontinuation of dostarlimab in 1 (0.2%) patient and resolved in all 3 patients.
Immune-related rash: Immune-related rash (rash, rash maculo-papular, rash macular, rash pruritic, pemphigoid, drug eruption, skin toxicity, toxic skin eruption) occurred in 31 (5.1%) patients, including Grade 3 in 9 (1.5%) patients receiving dostarlimab. The median time to onset of rash was 57 days (range 2 days to 1485 days). Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 9 (29.0%) patients experiencing rash. Rash led to discontinuation of dostarlimab in 1 (0.2%) patient and resolved in 24 (77.4%) patients.
Immune-related rash (rash, rash maculo-papular) occurred in 39 (16.2%) patients who received dostarlimab in combination with carboplatin-paclitaxel, including grade 2 (9.1%) and grade 3 (7.1%). Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 8 (20.5%) patients experiencing rash. Rash led to discontinuation in 3 (1.2%) patients and resolved in 38 (97.4%) patients experiencing rash.
Immune-related arthralgia: Immune-related arthralgia occurred in 34 (5.6%) patients. Grade 3 immune-related arthralgia was reported in 5 (0.8%) patients receiving dostarlimab. The median time to onset of arthralgia was 94.5 days (range 1 day to 840 days). Systemic corticosteroids (prednisone ≥40 mg per day or equivalent) were required in 3 (8.8%) patients experiencing arthralgia. Arthralgia led to discontinuation of dostarlimab in 1 (0.2%) patient and resolved in 19 (55.9%) patients experiencing arthralgia.
Infusion-related reactions: Infusion-related reactions including hypersensitivity occurred in 6 (1.0%) patients, including grade 2 (0.3%) and grade 3 (0.2%) infusion-related reactions. All patients recovered from the infusion-related reaction.
Immune checkpoint inhibitor class effects: There have been cases of the following adverse reactions reported during treatment with other immune checkpoint inhibitors which might also occur during treatment with dostarlimab: coeliac disease; pancreatic exocrine insufficiency.
Immunogenicity: In the GARNET study, anti-drug antibodies (ADA) were tested in 315 patients who received dostarlimab and the incidence of dostarlimab treatment-emergent ADAs was 2.5%. Neutralising antibodies were detected in 1.3% of patients. Co-administration with chemotherapy did not affect dostarlimab immunogenicity. In the RUBY study, of the 225 patients who were treated with dostarlimab in combination with chemotherapy and evaluable for the presence of ADAs, there was no incidence of dostarlimab treatment-emergent ADA or treatment‑emergent neutralising antibodies.
In the patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab.
Elderly population: Of the 605 patients treated with dostarlimab monotherapy in the GARNET study, 51.6% were under 65 years, 36.9% were 65 to less than 75 years, and 11.5% were 75 years or older. No overall differences in safety were reported between elderly (≥65 years) and younger patients (<65 years).
Of the 241 patients treated with dostarlimab in RUBY, 52.3% were younger than 65 years, 36.5% were aged 65 to less than 75 years, and 11.2% were 75 years or older. No overall differences in safety were observed between elderly (≥65 years) and younger patients (<65 years).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions. If any side effects are experienced, patients must be advised. This includes any side effects not listed. For adverse event reporting, call GlaxoSmithKline Limited at (852) 3189 8989 (Hong Kong) or (853) 2871 5569 (Macau), or send an email at HKAdverseEvent@gsk.com.