PACE 5-year data in CML:

ICLUSIG (ponatinib) delivered deep and durable efficacy1,2

PACE TRIAL DESIGN

PACE was a single-arm, open-label, international, multicenter, phase 2 trial studying ICLUSIG in adult patients with CML or Ph+ ALL that was resistant or intolerant to a prior kinase inhibitor, or who had T315I mutation (n=449).1,3

In PACE, patients received a starting dose of ICLUSIG 45 mg orally once daily (N=449; n=270 CP-CML, n=85 AP-CML, n=62 BP-CML, n=32 Ph+ ALL).1,3

Chart showing the study design for PACE. CP-CML patients were given a starting dose of 45mg. The median follow up time was 5 years.
aThree patients who had not received prior dasatinib or nilotinib did not have T315I confirmed at baseline and were not evaluable for efficacy.1
bDose reductions to 15 mg once daily or 30 mg once daily were applied to patients with and without MCyR, respectively, and were applied to manage AEs, or implemented proactively following an accumulation of AOEs.1,2
cResistance in CP-CML while on prior TKI therapy was defined as failure to achieve either a CHR (by 3 months), a minor cytogenetic response (by 6 months), or a MCyR (by 12 months). Patients with CP-CML who experienced a loss of response or development of a kinase domain mutation in the absence of a CCyR or progression to AP-CML or BP-CML at any time on prior TKI therapy were also considered resistant. Intolerance was defined as the discontinuation of prior TKI therapy due to toxicities despite optimal management in the absence of a CCyR in patients with CP-CML or MaHR for patients with AP-CML, BP-CML, or Ph+ ALL.1

 
Bar study icon.
  • At study completion, the median duration of follow-up for the trial (all cohorts) was 40.5 months (range: 0.1 months to 79.5 months)1
  • The major efficacy outcome measure (primary endpoint) for patients with CP-CML was MCyR by 12 months, which included CCyR and PCyR1,a
  • Dose reductions to 30 mg or 15 mg once daily were applied to manage adverse reactions, per protocol, or implemented proactively in 20132,b

aPrimary endpoint was MCyR by 12 months for CP-CML and MaHR by 6 months for AP-CML, BP-CML, or Ph+ ALL. Secondary endpoints included major molecular response (MMR), time to and duration of response, progression-free survival (PFS), overall survival (OS), and safety.2 

b15 mg once daily for CP-CML patients with MCyR, and 30 mg once daily for CP-CML patients without MCyR, AP-CML, and BP-CML patients.2

PATIENT CHARACTERISTICS

CP-CML patients in the PACE trial had highly-resistant disease—80% of patients were resistant* to prior TKI therapy and 24% had at least one BCR::ABL1 mutation1,2

Baseline characteristics of participants in the PACE Trial.

AT ENROLLMENT, FEW STUDY PATIENTS HAD PREVIOUSLY RESPONDED TO A PRIOR TKI3

Best response to any treatment prior to ICLUSIG2,a

26 percent of patients achieved MCyR or better. 3 percent of patients achieved MMR.

aMost recent regimen containing dasatinib or nilotinib.1,3

IN PACE, TKI-RESISTANT PATIENTS ACHIEVED DEEP, CLINICALLY SIGNIFICANT RESPONSES AND HIGH RATES OF MMR1

Proven long-term benefit in patients with TKI-resistant CP-CML (n=267)1

55 percent of patients achieved MCyR by 12 months (n=148/267). 40 percent of patients achieved MMR at any time (n=105/267).

ICLUSIG ACHIEVED A DEEP AND DURABLE RESPONSE OVER 5 YEARS IN CP-CML, 
TKI-RESISTANT, AND T315I PATIENTS1

Achieved MCyR by 12 months%^1

55% of the total CP-CML patient population achieved MCyR by 12 months. 51% of resistant/intolerant patients achieved MCyR by 12 months. 70% of T315i patients achieved MCyR by 12 months.
  • Median duration of treatment for CP-CML patients was 35 months1
In PACE, ICLUSIG provided durable, clinically meaningful responses in TKI-resistant CP-CML patients, including those with the T315I mutation.1 

CONSISTENT ESTIMATED OS/PFS THROUGH YEAR 5, EVEN IN PATIENTS WITH A T315I MUTATION2

Chart showing estimated OS/PFS through year 5, even in patients with T315i. Estimated OS at year 5 was 73% for the total CP-CML patient population. Estimated PFS at year 5 was 53% for the total CP-CML patient population.
Median OS and PFS were not reached2

ICLUSIG DEMONSTRATED EFFICACY IN AP- AND BP-CML PATIENTS WITH 
RESISTANT OR INTOLERANT ADVANCED DISEASE1

Efficacy of ICLUSIG in patients with resistant or intolerant advanced disease (includes R/I and T315I cohorts) in PACE1

Chart showing the efficacy of ICLUSIG in patients with resistant or intolerant advanced disease in PACE.
aPrimary endpoint for patients with AP-CML, BP-CML, and Ph+ ALL was MaHR by 6 months, which combines complete hematologic responses and no evidence of leukemia.1
bCHR: WBC ≤ institutional ULN, ANC ≥1000/mm3, platelets ≥100,000/mm3, no blasts or promyelocytes in peripheral blood, bone marrow blasts ≤5%, <5% myelocytes plus metamyelocytes in peripheral blood, basophils <5% in peripheral blood, no extramedullary involvement (including no hepatomegaly or splenomegaly).1

PATIENTS IN PACE ACHIEVED AND SUSTAINED RESPONSES1

Median time to MaHR1

Median time to MaHR for AP-CML patients was 0.8 months. For BP-CML patients it was 1 month.

Median duration of MaHR1

Median duration of MaHR for AP-CML patients was 14 months. For BP-CML patients it was 6.5 months.

An established safety profile CP-CML

PACE safety data

ICLUSIG (ponatinib) has a distinct inhibitory mechanism in CP-CML

Delve into ICLUSIG MOA

AOE=arterial occlusive events; AP-CML=accelerated-phase chronic myeloid leukemia; BP-CML=blast-phase chronic myeloid leukemia; CCyR=complete cytogenetic response; CI=confidence interval: CHR=complete hematologic response; CML=chronic myeloid leukemia; CP CML=chronic-phase chronic myeloid leukemia; ECOG PS=Eastern Cooperative Oncology Group performance status; MaHR=major hematologic response; MCyR=major cytogenetic response; MMR=major molecular response; OS=overall survival; PCyR=partial cytogenetic response; Ph+ ALL=Philadelphia chromosome-positive acute lymphoblastic leukemia; PFS=progression-free survival; QD=once daily; TKI=tyrosine kinase inhibitor.

IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE

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