Pharmacokinetics,
Efficacy & Safety of INQOVI

ASCERTAIN phase 3 crossover trial

The phase 3 crossover trial was designed to assess systemic decitabine exposure, demethylation activity, and safety between IV decitabine and INQOVI® (decitabine and cedazuridine) tablets. The trial allowed for intrapatient comparison in the first 2 randomized treatment cycles, and then assessment of the long-term efficacy and safety of INQOVI as a single arm.1,2

Phase 3 crossover design1

A chart demonstrating the Phase 3 ASCERTAIN crossover design

Open-label, randomized, 2-cycle, 2-sequence, crossover clinical trial in treatment-experienced or -naive patients with MDS, including CMML (International Prognostic Scoring System [IPSS] Intermediate-1, -2, or high-risk).1

  • Patients were allowed to have 1 prior cycle of decitabine or azacitidine, and there was no limit for body weight or surface area
  • Patients were randomized 1:1 to INQOVI (decitabine 35 mg/cedazuridine 100 mg) or IV decitabine 20 mg/m2 daily from day 1 through day 5 of each 28-day cycle
  • Patients received one agent in cycle 1 and then crossed over to receive the other agent in cycle 2
  • All patients received INQOVI after cycle 2, and treatment continued until disease progression or unacceptable toxicity
  • In the pooled safety population of phases 2 and 3, 61% of patients receiving INQOVI were exposed for ≥6 months and 24% were exposed for >1 year

Baseline characteristics of patients
in the phase 3 trial1

Baseline characteristics of patients in the Phase 3 ASCERTAIN trial Baseline characteristics of patients in the Phase 3 ASCERTAIN trial

aOne cycle only, per the exclusion criteria.

bDefined as documentation of ≥2 units of transfusion with 56 days of the first day of study treatment.

ECOG=Eastern Cooperative Oncology Group; RBC=red blood cell.

Proven efficacy results in ASCERTAIN phase 3 crossover trial1

Primary endpoint results

Orally administered INQOVI® (decitabine and cedazuridine) tablets demonstrated equivalent
systemic exposure to IV-administered decitabine.

99%

ratio of oral to IV 5-day decitabine AUC
(90% Cl: 93, 106)

  • This ratio is the geometric mean of the 5-day cumulative decitabine AUC between INQOVI
    and IV-administered decitabine when administered once daily for 5 consecutive days

Efficacy results in patients with MDS or CMML in phase 3 crossover trial (N=133)

21%

of patients achieved a complete response
(CR, 95% CI: 15, 29)

7.5 months

median duration of CR*
(range: 1.6-17.5)

*From start of CR until relapse or death.

4.3 months

median time to CR
(range: 2.1-15.2)

AUC=area under the curve; CI=confidence interval.

Transfusion dependence

53%

of the patients treated with INQOVI who were initially transfusion dependent achieved posttreatment RBC and platelet transfusion independence (30/57)

During any consecutive 56-day postbaseline period.

63%

of patients who initially were both RBC and platelet transfusion independent remained transfusion independent (48/76)

Safety results similar to IV decitabine1

Adverse reactions reported in ≥10% of patients in the
pooled phase 2 and phase 3 safety population

Chart showing select laboratory abnormalities in >20% of the pooled safety population
  • Safety results were similar to IV decitabine with no unexpected adverse reactions reported in the first 2 cycles1
  • 5% of patients taking INQOVI® (decitabine and cedazuridine) tablets discontinued due to an adverse reaction. The most frequent adverse reactions resulting in permanent discontinuation were febrile neutropenia (1%) and pneumonia (1%)1.
  • Clinically relevant adverse reactions in <10% of patients who received INQOVI included: acute febrile neutrophilic dermatosis (Sweet's syndrome) (1%) and tumor lysis syndrome (0.5%)1
  • Serious adverse reactions occurred in 68% of patients who received INQOVI. Serious adverse reactions in >5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%)1
  • Fatal adverse reactions occurred in 6% of patients, and included sepsis (1%), pneumonia (1%), respiratory failure (1%), septic shock (1%), and one case each of cerebral hemorrhage and sudden death1
  • Dose interruptions due to an adverse reaction occurred in 41% of patients who received INQOVI. Adverse reactions requiring dosage interruptions in >5% of patients who received INQOVI included neutropenia  (18%), febrile neutropenia (8%), thrombocytopenia (6%), and anemia (5%)1
  • Dose Reductions due to an adverse reaction occurred in 19% of patients who received INQOVI. Adverse reactions requiring dosage reductions in >2% of patients who received INQOVI included neutropenia (12%), anemia (3%), and thrombocytopenia (3%)1

aPlease see full Prescribing Information for complete list of adverse events occurring during all cycles.

bIncludes multiple adverse reaction terms.

cIncludes adverse reactions that occurred during all cycles, including during treatment with 1 cycle of intravenous decitabine.

Safety results similar to IV decitabine1

Select laboratory abnormalities (>20%) in pooled safety population1

A chart showing the adverse reactions reported in ≥ 10 percent of the pooled phase 2 and phase 3 safety population

aIncludes any lab abnormalities that worsened by ≥1 grades. Grades 3 to 4 include any lab abnormalities that worsened to grade 3 or grade 4.

bThe denominator used to calculate the rate varied from 103 to 107 for INQOVI cycle 1, from 102 to 106 for the IV decitabine cycle, and from 203 to 208 for INQOVI (all cycles) based on the number of patients with a baseline value and ≥1 posttreatment value.

Please see full Prescribing Information for chemistry lab safety parameters.

References: 1. INQOVI. Prescribing information. Taiho Oncology Inc; 2020. 2. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine: a phase 2, pharmacokinetic/pharmacodynamic, randomized, crossover study in MDS and CMML. Blood. doi:10.1182/blood.2019004143.

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