Redefine treatment for patients with newly diagnosed Ph+ ALL

The FIRST and ONLY FDA-APPROVED TKI for adults with NEWLY DIAGNOSED Ph+ ALL, in combination with chemotherapy1

PhALLCON was the first head-to-head phase 3 clinical trial in adults with newly diagnosed Ph+ ALL1,2

245 global participants were randomized 2:1 to receive ICLUSIG + chemotherapy or imatinib + chemotherapy in a study with a composite primary endpoint of MRD-negative CR1,2

Graphic of trial design for the PhALLCON trial, including inclusion and exclusion criteria for participants, trial groups, and primary, secondary, and additional endpoints.

Only patients who achieved the primary endpoint of MRD-negative CR or CRi at the end of induction could continue study treatment at the investigator’s discretion1

  • Single-agent therapy after chemotherapy for newly diagnosed Ph+ ALL is not an approved regimen1

*Following combination therapy, patients continued to receive ICLUSIG or imatinib as single-agent therapy until relapse from CR, progressive disease (PD), hematopoietic stem cell transplantation (HSCT), start of alternative therapy, or unacceptable toxicity.1
†MRD-negative CR was defined as ≤0.01% BCR::ABL1/ABL1 or undetectable BCR::ABL1 transcripts in cDNA with ≥10,000 ABL1 transcripts, and meeting criteria for CR.1 
‡EFS defined as dates of randomization until death due to any cause, failure to achieve CR by the end of induction, or relapse from CR.1

Reduced-intensity chemotherapy regimens

  • Induction (3 x 28-day cycles)1
    • Vincristine 1.4 mg/m2 (capped at 2 mg) intravenously (IV): Days 1,14
    • Dexamethasone 40 mg (<60 years), 20 mg (≥60 years) orally (PO): Days 1–4, 11–14
  • Consolidation (6 x 28-day cycles)1
    • Methotrexate 1000 mg/m2 (<60 years), 250 mg/m2 (≥60 years) IV: Day 1 on Cycles 4, 6, 8 
    • Cytarabine* 1000 mg/m2 (<60 years), 250 mg/m2 (≥60 years) IV: Days 1, 3, 5 on Cycles 5, 7, 9
  • Maintenance (11 x 28-day cycles)1
    • Vincristine 1.4 mg/m2 (capped at 2 mg/m2) IV: Day 1 of each cycle
    • Prednisone 200 mg PO (<60 years), 100 mg PO (≥60 to 69 years), 50 mg PO (≥70 years) on Days 1 to 5
       

CNS prophylaxis was administered on Day 1 and Day 14 of the 3 induction phase cycles and the first 3 consolidation phase cycles (total: 6 cycles, 12 intrathecal injections) and comprised a triple intrathecal injection of methotrexate, cytarabine, and corticosteroids. If patients moved to the maintenance phase directly from induction or before completing consolidation, they were still required to receive the complete course.2

*Every 12 hours.

ICLUSIG was studied in a diverse range of adults with newly diagnosed Ph+ ALL in PhALLCON1

Baseline patient and disease characteristics were well balanced across arms1,2

Baseline patient and disease characteristics for PhALLCON trial.
>1 in 3 patients were 60 years of age or older.
More than half of all patients had at least 1 CV comorbidity.

aPer protocol, patients were allowed to receive one cycle of optional prephase therapy excluding TKI prior to randomization.1

Significantly superior rate of MRD-negative CR with ICLUSIG vs imatinib at the end of induction (primary endpoint)1

In PhALLCON, ICLUSIG delivered more than double the rate of MRD-negative CR at the end of the 3-month induction phase1*

Two times rate of MRD-negative CR was achieved with ICLUSIG vs imatinib at the end of induction.
  • MRD-negative CR was defined as ≤0.01% BCR::ABL1, or undetectable BCR::ABL1 transcripts in cDNA with ≥10,000 ABL1 transcripts and meeting criteria for CR1

*Efficacy population included patients with Ph+ALL with baseline BCR::ABL dominant variant p190 and p210; 13 patients had atypical, missing, or unevaluable BCR::ABL1 assessment and were not included in the efficacy analysis.1,2
†Treatments were used in combination with chemotherapy.1

ICLUSIG delivered a higher rate of MRD negativity vs imatinib at the end of induction (additional endpoint)2*

18% more ICLUSIG patients achieved MRD negativity vs imatinib patients at the end of induction.
  • PhALLCON was designed to show a statistically significant difference between arms for MRD-negative CR; the trial was not designed to show a statistically significant difference between arms for MRD-negativity alone2

*MR4 rate is defined as the proportion of patients who achieved molecular response 4-log reduction or better (BCR::ABL1/ABL1 ≤0.01% with ABL1 ≥10,000 copies).2
†Treatments were used in combination with chemotherapy.1

Duration of complete remission and MRD negativity (additional endpoints)2*†

Duration of CR2

Graph showing duration of complete remission and MRD negativity (additional endpoints) in PhALLCON.

Duration of MRD negativity2

Graph showing probability of duration of MRD negativity in PhALLCON.

Study features 

  • Median duration of CR was not reached with ICLUSIG vs 19.4 months with imatinib. Median duration of MRD negativity was not reached with ICLUSIG vs not reached with imatinib2
  • The median duration of follow-up was 20.4 months (95% CI: 18.4, 23.9) with ICLUSIG and 18.1 months (95% CI: 13.9, 24.3) with imatinib1
  • Relapse from CR: 8.2% (n=10) of ICLUSIG patients vs 10.2% (n=5) of imatinib patients. Relapse from MRD negativity: 14% (n=8) of ICLUSIG patients vs 13.3% (n=2) of imatinib patients. Time of data cutoff (August 12, 2022)2
  • PhALLCON was designed to show a statistically significant difference between arms for MRD-negative CR; the trial was not designed to show a statistically significant difference between arms for duration of CR and MRD negativity2

*CR was defined as meeting all of the following for ≥4 weeks: <5% lymphoblasts in bone marrow, no lymphoblasts in blood, blood cell counts have normalized, and all signs and symptoms of ALL are gone. MRD negativity was defined as ≤0.01% BCR::ABL1, or undetectable BCR::ABL1 transcripts in cDNA with ≥10,000 ABL1 transcripts. MRD negativity data were not collected in patients progressing to stem cell transplant.2

†Complete remission is also known as complete response.

In adults with newly diagnosed Ph+ ALL, ICLUSIG + chemotherapy had a comparable safety profile to imatinib + chemotherapy1

Most common adverse reactions ≥20% in the PhALLCON study1

Chart of the most common adverse reactions in the PhALLCON study.

a Graded using CTCAE v5.0.1 
b Includes arthralgia, arthritis, back pain, flank pain, intervertebral disc degeneration, joint swelling, osteoarthritis, pain, neck pain, pain in extremity, pain of skin, sciatica, spinal pain, tendonitis, and tenosynovitis.1 
c Includes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain lower, abdominal pain upper, chronic gastritis, colitis, enteritis, enterocolitis, gastric ulcer, gastritis, gastroenteritis, gastrointestinal pain, gastroesophageal reflux disease, and helicobacter gastritis.1

ICLUSIG + chemotherapy safety profile in the PhALLCON study

Serious and fatal adverse reactions

  • Serious adverse reactions occurred in 63% of ICLUSIG patients and 57% of imatinib patients1,2
  • Serious adverse reactions (>2%) in ICLUSIG patients included febrile neutropenia (18%), pyrexia (6%), thrombocytopenia (4.3%), sepsis (3.7%), septic shock (3.7%), anemia (2.5%), hemorrhage (2.5%), neutropenia (2.5%), pancreatitis (2.5%), peripheral neuropathy (2.5%), pneumonia (2.5%), and acute kidney injury (2.5%)1
  • Fatal adverse reactions occurred in 6% of patients in both arms (ICLUSIG: 9 patients; imatinib: 5 patients). These events included sepsis in 6 (3.7%) ICLUSIG patients and 2 (2.4%) imatinib patients, sudden death, pneumonitis and respiratory failure in 1 (0.6%) ICLUSIG patient each, and pulmonary sepsis, depressed level of consciousness and pseudomembranous colitis in 1 (1.2%) imatinib patient each. One fatal TEAE was considered treatment-related in the imatinib arm (depressed level of consciousness)1,2

Discontinuations

  • Permanent discontinuation due to adverse reactions occurred in 13% of ICLUSIG patients. Adverse reactions resulting in permanent discontinuation in >2% of ICLUSIG patients included arterial occlusive events and sepsis1

Laboratory abnormalities

  • The most common Grade 3 or 4 laboratory abnormalities (>20%) are decreased white blood cell count, decreased neutrophil cell count, decreased platelet count, decreased lymphocyte cell count, decreased hemoglobin, increased lipase, and increased ALT1

Clinically relevant

  • Clinically relevant adverse reactions in ≤10% of ICLUSIG patients included urinary tract infection (10%), arterial occlusive events (6%), cardiac failure (6%), and acute kidney injury (4.3%)1

In PhALLCON, ICLUSIG demonstrated comparable safety outcomes with imatinib, including rates and severity of AOEs and VTEs1,2

  • The rate of TE-VTEs was 11.7% in ICLUSIG patients vs 12.3% in imatinib patients2
  • The rate of TE-AOEs was 2.5% in ICLUSIG patients vs 1.2% in imatinib patients2

Response-based dosing with ICLUSIG + chemotherapy for adults with newly diagnosed Ph+ ALL1

A starting dose of ICLUSIG 30 mg can be reduced to 15 mg once a patient achieves a meaningful response1*†

Response-based dosing strategy with ICLUSIG + chemotherapy for adults with newly diagnosed Ph+ ALL.
  • See Table 1 of the PI for the complete recommended dosage modifications for ARs depending on severity

*Please note the recommended starting dose of ICLUSIG monotherapy for Ph+ ALL for whom no other kinase inhibitors are indicated or T3151-positive Ph+ ALL is 45 mg once daily.1
† Please note the recommended starting dose of ICLUSIG for CML is 45 mg once daily. Patients with CP-CML can reduce to 15 mg orally once daily upon achievement of ≤1% BCR-ABL1. Consider reducing the dose of ICLUSIG for patients with AP-CML who have achieved a major cytogenetic response.1
‡One cycle is 28 days.1

ICLUSIG: One pill, once a day, with or without food.

ICLUSIG achieved deep remission in front-line Ph+ ALL

PhALLCON study efficacy

ICLUSIG demonstrated comparable safety profile to imatinib in head-to-head study

PhALLCON safety data

ALL=acute lymphoblastic leukemia; ALT=alanine aminotransferase; AOEs=arterial occlusive events; AP-CML=accelerated-phase chronic myeloid leukemia; AR=adverse reaction; cDNA=complementary DNA; CI=confidence interval; CML=chronic myeloid leukemia; CNS=central nervous system; CP-CML=chronic-phase chronic myeloid leukemia; CR=complete remission; CRi=incomplete hematologic response; CTCAE=Common Terminology Criteria for Adverse Events; CV=cardiovascular; ECOG PS=Eastern Cooperative Oncology Group performance status; EFS=event-free survival; MRD=minimal residual disease; MR=molecular response; NE=not evaluable; PI=Prescribing Information; Ph+ ALL=Philadelphia chromosome-positive acute lymphoblastic leukemia; QD=once daily; TEAE=treatment-emergent adverse event; TE-AOEs=treatment-emergent arterial occlusive events; TE-VTEs=treatment-emergent venous thromboembolic events; TKI=tyrosine kinase inhibitor; VTEs=venous thromboembolic events.

IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE

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