COPIKTRA

COPIKTRA — duvelisib capsule
Secura Bio, Inc.

1 INDICATIONS AND USAGE

​ COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) after at least two prior therapies.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing

The recommended dose of COPIKTRA is 25 mg administered as oral capsules twice daily (BID) with or without food. A cycle consists of 28 days. The capsules should be swallowed whole. Advise patients not to open, break, or chew the capsules.

Advise patients that if a dose is missed by fewer than 6 hours, to take the missed dose right away and take the next dose as usual. If a dose is missed by more than 6 hours, advise patients to wait and take the next dose at the usual time.

2.2 Recommended Prophylaxis

Provide prophylaxis for Pneumocystis jirovecii (PJP) during treatment with COPIKTRA. Following completion of COPIKTRA treatment, continue PJP prophylaxis until the absolute CD4+ T cell count is greater than 200 cells/µL.

Withhold COPIKTRA in patients with suspected PJP of any grade, and discontinue if PJP is confirmed.

Consider prophylactic antivirals during COPIKTRA treatment to prevent cytomegalovirus (CMV) infection including CMV reactivation.

2.3 Dose Modifications for Adverse Reactions

Manage toxicities per Table 1 with dose reduction, treatment hold, or discontinuation of COPIKTRA.

Table 1. COPIKTRA Dose Modifications and Toxicity Management

Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase;
CMV = cytomegalovirus; DRESS = drug reaction with eosinophilia and systemic systems; PCR = polymerase chain reaction; PJP = Pneumocystis jirovecii; pneumonia; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal
Toxicity	Adverse Reaction Grade	Recommended Management
Nonhematologic Adverse Reactions
Infections	Grade 3 or higher infection	Withhold COPIKTRA until resolved Resume at the same or reduced dose (see Table 2)
	Clinical CMV infection or viremia (positive PCR or antigen test)	Withhold COPIKTRA until resolved Resume at the same or reduced dose (see Table 2) If COPIKTRA is resumed, monitor patients for CMV reactivation (by PCR or antigen test) at least monthly
	PJP	For suspected PJP, withhold COPIKTRA until evaluated For confirmed PJP, discontinue COPIKTRA
Non-infectious Diarrhea or colitis	Mild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and responsive to antidiarrheal agents, OR Asymptomatic (Grade 1) colitis	No change in dose Initiate supportive therapy with antidiarrheal agents as appropriate Monitor at least weekly until resolved
	Mild/moderate diarrhea (Grade 1-2, up to 6 stools per day over baseline) and unresponsive to antidiarrheal agents	Withhold COPIKTRA until resolved Initiate supportive therapy with enteric acting steroids (e.g., budesonide) Monitor at least weekly until resolved Resume at a reduced dose (see Table 2)
	Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR Severe diarrhea (Grade 3, >6 stools per day over baseline)	Withhold COPIKTRA until resolved Initiate supportive therapy with enteric acting steroids (e.g., budesonide) or systemic steroids Monitor at least weekly until resolved Resume at a reduced dose (see Table 2) For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue COPIKTRA
	Life-threatening	Discontinue COPIKTRA
Cutaneous reactions	Grade 1-2	No change in dose Initiate supportive care with emollients, anti-histamines (for pruritus), or topical steroids Monitor closely
	Grade 3	Withhold COPIKTRA until resolved Initiate supportive care with emollients, anti-histamines (for pruritus), or topical steroids Monitor at least weekly until resolved Resume at reduced dose (see Table 2) If severe cutaneous reaction does not improve, worsens, or recurs, discontinue COPIKTRA
	Life-threatening	Discontinue COPIKTRA
	SJS, TEN, DRESS (any grade)	Discontinue COPIKTRA
Pneumonitis without suspected infectious cause	Moderate (Grade 2) symptomatic pneumonitis	Withhold COPIKTRA Treat with systemic steroid therapy If pneumonitis recovers to Grade 0 or 1, COPIKTRA may be resumed at reduced dose (see Table 2) If non-infectious pneumonitis recurs or patient does not respond to steroid therapy, discontinue COPIKTRA
	Severe (Grade 3) or life-threatening pneumonitis	Discontinue COPIKTRA Treat with systemic steroid therapy
ALT/AST elevation	3 to 5 × upper limit of normal (ULN) (Grade 2)	Maintain COPIKTRA dose Monitor at least weekly until return to < 3 × ULN
	> 5 to 20 × ULN (Grade 3)	Withhold COPIKTRA and monitor at least weekly until return to < 3 × ULN Resume COPIKTRA at same dose (first occurrence) or at a reduced dose for subsequent occurrence (see Table 2)
	> 20 × ULN (Grade 4)	Discontinue COPIKTRA
Hematologic Adverse Reactions
Neutropenia	Absolute neutrophil count (ANC) 0.5 to 1.0 Gi/L	Maintain COPIKTRA dose Monitor ANC at least weekly
	ANC less than 0.5 Gi/L	Withhold COPIKTRA. Monitor ANC until > 0.5 Gi/L Resume COPIKTRA at same dose (first occurrence) or at a reduced dose for subsequent occurrence (see Table 2)
Thrombocytopenia	Platelet count 25 to < 50 Gi/L (Grade 3) with Grade 1 bleeding	No change in dose Monitor platelet counts at least weekly
	Platelet count 25 to < 50 Gi/L (Grade 3) with Grade 2 bleeding or Platelet count < 25 Gi/L (Grade 4)	Withhold COPIKTRA Monitor platelet counts until ≥ 25 Gi/L and resolution of bleeding (if applicable) Resume COPIKTRA at same dose (first occurrence) or resume at a reduced dose for subsequent occurrence (see Table 2)

Recommended dose modification levels for COPIKTRA are presented in Table 2.

Table 2. Dose Modification Levels

Dose Level	Dose
Initial Dose	25 mg twice daily
Dose Reduction	15 mg twice daily
Subsequent Dose Modification	Discontinue COPIKTRA if patient is unable to tolerate 15 mg twice daily.