OPTIC trial: Optimize ICLUSIG (ponatinib) efficacy with a response-based dosing strategy1

ICLUSIG achieved and maintained a clinically meaningful depth of response with a 45 mg → 15 mg dose reduction upon achievement of ≤1% BCR::ABL1IS in patients with CP-CML1

OPTIC TRIAL DESIGN: Utilizing a response-based dosing strategy with ICLUSIG

OPTIC is an ongoing, open-label, multicenter, randomized study designed to evaluate ICLUSIG across multiple response-based dosing regimens for patients with CP-CML.1,2 A total of 282 patients received ICLUSIG and were divided into 3 cohorts: The first cohort (n=94) received a starting dose of 45 mg, the second (n=94) received a starting dose of 30 mg, and the third (n=94) received a starting dose of 15 mg. Patients in cohorts 1 and 2 were reduced to 15 mg daily upon achievement of ≤1% BCR::ABL1IS. The primary endpoint for OPTIC is ≤1% BCR::ABL1IS at 12 months.2

OPTIC Trial design. CP-CML patient started off at 45 mg, 30 mg, and 15 mg doses and were monitored over a 24 month period.
Dose reductions were utilized in response to adverse reactions.1
Patients receiving 15 mg had their dose reduced to 10 mg QD.1

aResistance in CP-CML while on a prior TKI therapy was defined as failure to achieve either a CHR (by 3 months), a minor cytogenetic response (by 6 months), or a major cytogenetic response (by 12 months), or development of a new BCR::ABL1 kinase domain mutation or new clonal evolution.

PATIENT CHARACTERISTICS REVEAL HIGH TKI RESISTANCE AND MUTATIONS 

Demographic and disease characteristics in OPTIC1,2

Patient characteristics at entry of OPTIC.

ICLUSIG 45 mg → 15 mg: The path to maximizing benefit and mitigating risk1

ICLUSIG demonstrated response rates (≤1% BCR::ABL1IS) at 12 months, irrespective of mutation status2

Results from OPTIC demonstrate a benefit in a highly-resistant CP-CML population across dosing cohorts. However, optimal benefit:risk outcomes occurred in the cohort with a 45 mg starting dose that reduced to 15 mg upon achievement of ≤1% BCR::ABL1IS.1 The recommended starting dose is 45 mg orally once daily with a reduction to 15 mg orally once daily upon achievement of ≤1% BCR::ABL1IS.  Patients with loss of response can re-escalate the dose of ICLUSIG to a previously tolerated dose of 30 mg or 45 mg orally once daily.2

Patients with ≤1% BCR::ABL1IS at 12 months2 (primary endpoint)

44% of patients without T315i achieved less than or equal to 1% BCR-ABL1 at 12 months. 44% of patient with T315i achieved less than or equal to 1% BCR-ABL1 at 12 months.
aITT population (N=93) defined as patients who had b2a2/b3a2 BCR::ABL1 transcripts.2
bThe primary endpoint was ≤1% BCR::ABL1IS rate at 12 months. Defined as a ≤1% ratio of BCR::ABL1 to ABL transcripts on the International Scale (ie, ≤1% BCR::ABL1IS); patients must have the b2a2/b3a2 (p210) transcript), in peripheral blood measured by qRT PCR.2 
c Of the 93 patients, 2 did not have a baseline mutation assessment and were excluded from the response by mutation analysis.2

DURABLE RESPONSE WAS OBSERVED AT A REDUCED DOSE OF 15 mg2

Median duration of follow-up in the 45 mg→15 mg arm was 27.0 months2

62 percent of patients (n=28/45) maintained response at a reduced dose of 15 mg. 100 percent of patients (n=28/28) who maintained less than or equal to 1 percent BCR-ABL 1 at 15 mg did for greater or equal to 90 days.
aPatients who achieved ≤1% BCR::ABL1 at any time.

ESTIMATED OS AND PFS DATA FOR OPTIC WITH A RESPONSE-BASED DOSING STRATEGY1

Graphs showing estimated OS and PFS data in the 45 mg cohort.

ICLUSIG safety profile in the OPTIC Trial

ICLUSIG safety profile: OPTIC Trial

Learn to identify patients with CP-CML who are appropriate for ICLUSIG

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BCR::ABL1IS=BCR::ABL1 international scale; CP-CML=chronic-phase chronic myeloid leukemia; ECOG PS=Eastern Cooperative Oncology Group performance status; ITT=intent-to-treat; OS=overall survival; PFS=progression-free survival; TKI=tyrosine kinase inhibitor; QD=once a day; qRT PCR=quantitative reverse transcriptase polymerase chain reaction. 

IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE

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