OPTIC: A trial built with an optimized dosing strategy to manage tolerability without compromising efficacy1

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

OPTIC is an open-label, multicenter, randomized study that employs a dose-reduction strategy aiming to maximize the benefit of ICLUSIG while helping to mitigate risk in patients with CP-CML who are resistant to at least 2 prior TKIs or have the T315I mutation. The primary endpoint for OPTIC is ≤1% BCR::ABL1IS at 12 months.1

OPTIC Trial design. Patients with CP-CML started off at 45 mg, 30 mg, or 15 mg, and 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

The 5-year data provide an update on the long-term efficacy and safety profile of ICLUSIG in this setting and aim to provide more robust data on the best approaches for managing these patients over an extended period of time.

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.

Primary Analysis: ICLUSIG achieved and maintained a clinically meaningful depth of response1

ICLUSIG demonstrated response rates (≤1% BCR::ABL1IS) at 12 months, regardless of mutation status. The median duration of follow-up for the total population was 32 months (range, 1-57)1, 2

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::ABL1IS at 12 months. 44% of patient with T315I achieved less than or equal to 1% BCR::ABL1IS at 12 months.
  • Median duration of follow-up in the 45mg→15mg cohort was 27.0 months2
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

Maintained Response

56% of patients (n=25/45) maintained response at a reduced dose of 15 mg for at least 1 year. 64% of these patients (n=16/25) maintained response for greater than 60 months.

aPatients who achieved ≤1% BCR::ABL1IS at any time.

Long-Term Efficacy Data: More than half of patients had a response by 5 years in the 45 mg → 15 mg cohort2

Response of patients by 12 months and 60 months in the 45 mg→15 mg cohort receiving ICLUSIG following ≥2 prior TKIs2 

Bar chart showing percentage of patients who achieved 1% BCR-::ABL1IS levels. Two bars display: 52% achieving it by 12 months. 60% achieving it by 60 months.
  • Median duration of follow-up for the 45mg→15mg cohort was 72.9 months (range: 0.5-106.3 months)
Study Limitations: The OPTIC 5-year follow-up analysis was a planned, exploratory, post hoc analysis. It was not powered to detect differences across subgroups. Results are presented descriptively.2
 
aResponse by each time point means the best outcome up to each time point after randomization.
bAnalysis conducted in the intent-to-treat population. 
cData cutoff date: May 15, 2024. 
d29% of patients in the 45 mg→15 mg cohort remained on therapy, with a median follow-up of 78 months. 
eThe number of patients with ≤1% BCR::ABL1IS was counted on a cumulative basis by each time point, and a patient with response was counted only once. Percentages are based on the number of patients in each cohort as the denominator.

Deep, durable efficacy achieved with ICLUSIG

As of the 5-year follow-up data cutoff, the median duration of ≤1% BCR::ABL1IS had not been reached

  • In the 45 mg→15 mg cohort (n=93), 56 patients achieved ≤1% BCR::ABL1
    • 45 of the 56 patients had a dose reduction to 15 mg after achieving response
    • 68.9% (n=31) of these patients maintained their response at the time of the 5-year data follow-up cutoff 
Bar chart showing depth of response by 60 months for BCR::ABL1IS levels. Three bars display: 46% achieving MMR, 24% achieving MR4, and 13% achieving MR4.5.
aResponse by each time point means the best outcome up to each time point after randomization. 
bAnalysis conducted in the intent-to-treat population.

Long-term efficacy with ICLUSIG in patients carrying T315I mutation

  • 64% of patients with T315I mutation achieved BCR::ABL1 levels of 1% or less by 60 months2

ICLUSIG safety profile in the OPTIC Trial

ICLUSIG safety profile: OPTIC Trial

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

Explore patient profiles

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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