Efficacy & Safety of INQOVI

ASCERTAIN trial design

The phase 3 crossover trial was designed to assess systemic decitabine exposure, demethylation activity, and safety between IV decitabine and INQOVI. The trial allowed for intrapatient comparison in the first 2 randomized treatment cycles, 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

Phase 3, open-label, randomized, 2-cycle,
2-sequence, crossover trial design 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 1 prior cycle of decitabine or azacitidine, with no limit for body weight or surface area
  • Randomized 1:1 to INQOVI® or IV decitabine 20 mg/m2 daily from day 1 through day 5 of each
    28-day cycle
  • Received one agent in cycle 1 and then crossed over to receive the other agent in cycle 2
  • All 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 patient characteristics1

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

After taking INQOVI, 20% (27/133) of patients went on to receive stem cell transplantation.1

aOne cycle only, per the exclusion criteria.

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

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

The only oral HMA with equivalent systemic exposure to IV decitabine1

Equivalent Systemic Exposure

Primary endpoint results

Orally administered INQOVI demonstrated equivalent
systemic exposure to IV-administered decitabine.

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

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)

Complete Response (CR)

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

Median Time to CR
(range: 2.1-15.2)

Median Duration of CR*
(range: 1.6-17.5)

*From start of CR until relapse or death.

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

Transfusion Independence

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

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

†During any consecutive 56-day postbaseline period.

Safety profile 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 profile similar to IV decitabine with no unexpected adverse reactions reported in the first 2 cycles1

  • Incidence of cytopenias was slightly higher in INQOVI during cycle 1 compared to IV decitabine
  • 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%)
  • 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%)
  • Fatal adverse reactions occurred in 6% of patients, and included sepsis (1%), pneumonia (1%), respiratory failure (1%), septic shock (1%), and 1 case each of cerebral hemorrhage and sudden death
  • 5% of patients discontinued treatment with INQOVI due to an adverse reaction
  • 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%)
  • Dose reductions due to an adverse reaction occurred in 19% of patients who received INQOVI. Adverse reactions requiring dosage reductions in >2% of patients included neutropenia (12%), anemia (3%), and thrombocytopenia (3%)

cPlease see full Prescribing Information for complete list of adverse eventoccurring during all cycles.

dIncludes multiple adverse reaction terms.

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

Select hematologic lab abnormalities1

>20% in the pooled safety population

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

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

gThe 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 [package insert]. Princeton, NJ: Taiho Oncology, Inc.; 2022 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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