Copanlisib is an inhibitor of MATE2-K (IC50: 0.09 μM). Based on the PK of copanlisib,inhibition may occur after copanlisib infusion at approved recommended dosage. The clinical significance of this potential inhibition on plasma concentrations of concomitantly administered drugs that are MATE2-K substrates is unknown. 

 

13 NONCLINICAL TOXICOLOGY 

 

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 

 

Carcinogenicity studies have not been conducted with copanlisib.

 

Copanlisib did not cause genetic damage in in vitro or in vivo assays.

 

Fertility studies with copanlisib were not conducted; however, adverse findings in male and female reproductive systems were observed in the repeat dose toxicity studies. Findings in the male rats and/or dogs included effects on the testes (germinal epithelial degeneration, decreased weight, and/or tubular atrophy), epididymides (spermatic debris, decreased weight, and/or oligospermia/aspermia), and prostate (reduced secretion and/or decreased weight). Findings in female rats included effects on ovaries (hemorrhage, hemorrhagic cysts, and decreased weight), uterus (atrophy, decreased weight), vagina (mononuclear infiltration), and a dose-related reduction in the numbers of female rats in estrus.

 

14 CLINICAL STUDIES 

 

14.1 Relapsed Follicular Lymphoma 

 

The efficacy of ALIQOPA was eva luated in a single-arm, multicenter, phase 2 clinical trial (NCT 01660451) CHRONOS-1 in a total of 142 subjects, which included 104 subjects with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. Patients must have received rituximab and an alkylating agent. Baseline patient characteristics are summarized in Table 4. The most common prior systemic therapies were chemotherapy in combination with anti-CD20 immunotherapy (89%), chemotherapy alone (41%), and anti-CD20 immunotherapy alone (37%). In CHRONOS-1, 34% of patients received two prior lines of therapy and 36% received three prior lines of therapy. 

 

Table 4: Baseline Patient Characteristics (Follicular Lymphoma) 

 

Characteristics 

 

ALIQOPA

N=104 

 

Age, years; median (range)

 

62 (25 to 81)

 

Caucasian 

 

83%

 

 

Male

 

52%

 

ECOG performance status (0 or 1)

 

96%

 

Number of prior therapies; median (range)

 

3 (2 to 8)

 

Time since diagnosis, years; median (range)

 

5.8 (0.75 to 33.9)

 

Percent of patients refractory* to:

 

last regimen

 

62%

 

last anti-CD20 immunotherapy

 

57%

 

last alkylating agent

 

last combination anti-CD20 immunotherapy and alkylating agent 

 

38%

 

41%

 

*Refractory: No response or progression of disease within six months of last treatment.