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::ABL115 in patients with chronic-phase chronic myeloid leukemia1
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
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.
Dose reductions (45 mg QD → 30 mg QD, 30 mg QD → 15 mg QD) were permitted in patients who experienced adverse reactions.
aResistance in CP-CML while on a prior TKI therapy was defined as failure to achieve either a CHR (by 3 months), a minor cytogenic response (by 6 months), a major cytogenic response (by 12 months), or development of a new BCR::ABL1IS kinase domain mutation or new clonal evolution.
BCR::ABL1IS=BCR::ABL1 International Scale; CHR=complete hematologic response; CP-CML=chronic-phase chronic myeloid leukemia; ECOG PS=Eastern Cooperative Oncology Group performance status; QD=once daily; TKI=tyrosine kinase inhibitor.
PATIENT CHARACTERISTICS REVEAL HIGH TKI RESISTANCE AND MUTATIONS
Demographic and disease characteristics in OPTIC1,2
BCR::ABL1IS=BCR::ABL1 International Scale; ECOG=Eastern Cooperative Oncology Group; TKI=tyrosine kinase inhibitor.
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)
- Median duration of follow-up in the 45mg→15mg cohort was 27.0 months2
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
cOf the 93 patients, 2 did not have a baseline mutation assessment and were excluded from the response by mutation analysis.2
BCR::ABL1IS=BCR::ABL1 International Scale; CI=confidence interval; ITT=intent-to-treat; TKI=tyrosine kinase inhibitor
Long-Term efficacy data: More than half of patients had a response by 5 years in the 45 mg → 15 cohort2
In the 45 mg→15 mg cohort, patients had their dose reduced from 45 mg to 15 mg once response was achieved regardless of amount of time on treatment.
Response of patients by 12 months and 60 months in the 45 mg→15 mg cohort receiving ICLUSIG following ≥2 prior TKIs
- Median duration of follow-up for the 45 mg→15 mg 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
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.
BCR::ABL1IS=BCR::ABL1 International Scale; TKI=tyrosine kinase inhibitor
Deep, durable efficacy achieved with ICLUSIG
Long-term molecular response by 60 months in the 45 mg→15 mg cohort3
- 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::ABL1IS
- 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
bAnalysis conducted in the intent-to-treat population.
AE=adverse events; BCR::ABL1IS=BCR::ABL1 International Scale; CML=chronic myeloid leukemia; MMR=major molecular response; MR=molecular response.
If your patients with CML also have a T315I mutation:
- 64% of patients with T315I mutation achieved BCR::ABL1IS levels of 1% or less by 60 months2
- Ponatinib (ICLUSIG) is recommended as a treatment option by the National Comprehensive Cancer Network® (NCCN®) treatment guidelines for certain patients with T315I mutation4