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 the general patient population.
The safety data reflect exposure to ALIQOPA in 168 adults with follicular lymphoma and other hematologic malignancies treated with ALIQOPA 60 mg or 0.8 mg/kg equivalent in clinical trials. The median duration of treatment was 22 weeks (range 1 to 206 weeks).
Serious adverse reactions were reported in 44 (26%) patients. The most frequent serious adverse reactions that occurred were pneumonia (8%), pneumonitis (5%) and hyperglycemia (5%). The most common adverse reactions (≥20%) were hyperglycemia, diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory tract infections, and thrombocytopenia.
Adverse reactions resulted in dose reduction in 36 (21%) and discontinuation in 27 (16%) patients. The most common reasons for dose reduction were hyperglycemia (7%), neutropenia (5%), and hypertension (5%). The most common reasons for drug discontinuation were pneumonitis (2%) and hyperglycemia (2%).
Table 2 provides the adverse reactions occurring in at least 10% of patients receiving ALIQOPA monotherapy, and Table 3 provides the treatment-emergent laboratory abnormalities in ≥20% of patients and ≥4% of Grade ≥3 treated with ALIQOPA.
Table 2: Adverse Reactions Reported in ≥10% of Patients with Follicular Lymphoma and Other Hematological Malignancies Treated with ALIQOPA
ADVERSE REACTIONS
Copanlisib
N = 168
Any Grade
n (%)
Grade 3
n (%)
Grade 4
n (%)
Metabolism and nutrition disorders
Hyperglycemia
90 (54%)
56 (33%)
10 (6%)
Blood and lymphatic system disorders
Leukopenia
61 (36%)
20 (12%)
26 (15%)
Neutropenia (including febrile neutropenia)
53 (32%)
16 (10%)
26 (15%)
Thrombocytopenia
37 (22%)
12 (7%)
2 (1%)
General disorders and administration site conditions
Decreased general strength and energy (includes fatigue and asthenia)
61 (36%)
6 (4%)
0
Gastrointestinal disorders
Diarrhea
60 (36%)
8 (5%)
0
Nausea
43 (26%)
1 (<1%)
0
Stomatitis (includes oropharyngeal erosion and ulcer, oral pain)
24 (14%)
3 (2%)