IMBRUVICA Rx

Mantle Cell Lymphoma

The safety and efficacy of Imbruvica in patients with MCL who have received at least 1 prior therapy were evaluated in Study 1104 (ClinicalTrials.gov Identifier: NCT01236391), an open-label, multi-center, single-arm trial of 111 previously treated patients. The primary endpoint was investigator-assessed overall response rate (ORR).

Findings showed an ORR of 65.8% (95% CI, 56.2-74.5), with 17.1% of patients having a complete response and 48.6% of patients having a partial response. Median duration of response (DoR) was 17.5 months (95% CI, 15.8-NE). Median time to response was 1.9 months.

Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

The safety and efficacy of IMBRUVICA in patients with CLL/SLL were demonstrated in 1 uncontrolled trial and 5 randomized, controlled trials.

Study 1102 (ClinicalTrials.gov Identifier: NCT01105247)

• Open-label, multicenter trial conducted in 48 previously treated CLL patients.
• Imbruvica was administered orally at 420mg once daily until disease progression or unacceptable toxicity.
• The ORR was 58.3% (95% CI, 43.2-72.4), all partial responses. 
• None of the patients achieved a complete response.
• The DoR ranged from 5.6 to 24.2+ months; median DoR was not reached.

RESONATE (ClinicalTrials.gov Identifier: NCT01578707)

• Randomized, multicenter, open-label, phase 3 study of Imbruvica vs ofatumumab conducted in 391 patients with previously treated CLL or SLL.
• Compared with ofatumumab, Imbruvica significantly improved progression free survival (PFS; hazard ratio [HR] for progression or death, 0.22 [95% CI, 0.15-0.32]; P <.001) and overall survival (OS; HR for death, 0.43 [95% CI, 0.24-0.79]; P =.005).
• 63 month follow-up: median PFS was 44.1 months for Imbruvica and 8.1 months for ofatumumab; ORR was 87.2% and 22.4%, respectively.
• Similar effects seen in patients with del 17p CLL/SLL.

RESONATE-2 (ClinicalTrials.gov Identifier: (NCT01722487)

• Randomized, multicenter, open-label, phase 3 study of Imbruvica vs chlorambucil conducted in 269 patients with treatment naïve CLL or SLL who were 65 years of age or older. 
• Imbruvica significantly prolonged PFS by reducing the risk of progression or death by 84% vs chlorambucil (hazard ratio [HR] 0.16, 95% CI, 0.09-0.28). 
• Imbruvica was also associated with a significantly higher ORR (82.4%) vs chlorambucil (35.3%). 
• A total of 5 patients achieved a complete response in the Imbruvica arm vs 2 patients in the chlorambucil arm.
• 55 month follow-up: median PFS was not reached in the Imbruvica arm.

HELIOS (ClinicalTrials.gov Identifier: NCT01611090)

• Randomized, multicenter, double-blind, phase 3 trial that evaluated Imbruvica in combination with bendamustine and rituximab (BR) vs placebo plus BR in relapsed/refractory patients with CLL/SLL (N=578).
• Imbruvica plus BR demonstrated an 80% reduction in the risk of progression or death (HR, 0.20, 95% CI, 0.15-0.28) vs placebo plus BR.
• ORR was 82.7% for Imbruvica plus BR and 67.8% for placebo plus BR.

iLLUMINATE (ClinicalTrials.gov Identifier: NCT02264574)

• Randomized, multicenter, phase 3 study of Imbruvica in combination with obinutuzumab vs chlorambucil in combination with obinutuzumab conducted in patients with treatment naïve CLL or SLL (N=229).
• Treatment with Imbruvica + obinutuzumab led to a significant improvement in PFS vs chlorambucil + obinutuzumab after a median follow-up of 31 months (median not evaluable [NE] vs 19 months; hazard ratio [HR] 0.23, 95% CI, 0.15-0.37; P <.0001).
• For patients with high-risk disease (17p deletion/TP53 mutation, 11q deletion, or unmutated IGHV), the PFS HR was 0.15 (95% CI, 0.09-0.27).  
• ORR was 88.5% in the Imbruvica arm vs 73.3% in the chlorambucil arm.

E1912 (ClinicalTrials.gov Identifier: NCT02048813)

• Randomized, multicenter, phase 3 study of Imbruvica in combination with rituximab vs standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy conducted in adult patients who were 70 years or younger with previously untreated CLL or SLL requiring systemic therapy.
• At 37 months, treatment with Imbruvica plus rituximab was associated with a statistically significant improvement in PFS when compared with the FCR arm (HR 0.34; 95% CI, 0.22-0.52; P <.0001). 
• 49 month follow-up: median OS was not reached with a total of 23 deaths; 11 (3%) in the Imbruvica plus rituximab and 12 (7%) in the FCR treatment arms.

Waldenström’s Macroglobulinemia

The safety and efficacy of Imbruvica in patients with WM were demonstrated in 2 single-arm trials and 1 randomized, controlled trial.

Study 1118  (ClinicalTrials.gov Identifier: NCT01614821) 

• Open-label, multicenter, single-arm trial conducted in 63 previously treated patients with WM.
• Imbruvica was administered orally at 420mg once daily until disease progression or unacceptable toxicity.
• Response rate was 61.9% (95% CI, 48.8-73.9): 0 with complete response (CR), 11.1% with very good partial response (VGPR), 50.8% with partial response (PR).
• Median DoR: NE (2.8+, 18.8+).
• Median time to response was 1.2 months (range, 0.7-13.4 months).

INNOVATE Monotherapy Arm

• 31 patients with previously treated WM who failed prior rituximab-containing therapy and received single-agent Imbruvica.
• 61 month follow-up: response rate was 77% (0% CR, 29% VGPR, 48% PR).
• Median DoR: 33 months (range, 2.4 to 60.2+ months).

INNOVATE (ClinicalTrials.gov Identifier: NCT02165397)

• Randomized, double-blind, placebo-controlled, phase 3 study of Imbruvica or placebo in combination with rituximab conducted in treatment naïve or previously treated patients with WM (N=150).
• At 63 months, patients treated with Imbruvica + rituximab experienced an 75% reduction in relative risk of disease progression or death compared with those treated with placebo + rituximab (hazard ratio 0.25 [95% CI, 0.15-0.42); P <.0001). 
• Rate of response was greater in the Imbruvica + rituximab group compared with placebo + rituximab (76% vs 31%, respectively; P <.0001).

Marginal Zone Lymphoma

The safety and efficacy of Imbruvica in MZL were evaluated in Study 1121 (ClinicalTrials.gov Identifier: NCT01980628), an open-label, multicenter, single-arm trial of patients who received at least 1 prior therapy (N=63). In these patients, ORR was 46% (95% CI, 33.4-59.1) with 3.2% of patients achieving CR and 42.9% achieving PR. Median time to response was 4.5 months (range, 2.3 to 16.4 months). Overall response rates were 46.9%, 41.2%, and 50.0% for the 3 MZL subtypes (MALT, nodal, splenic), respectively.

Study 1129 (ClinicalTrials.gov Identifier: NCT02195869)

• The safety and efficacy of Imbruvica in cGVHD were evaluated in an open-label, multicenter, single-arm trial of 42 patients with cGVHD after failure of first line corticosteroid therapy and requiring additional therapy.
• After receiving Imbruvica 420mg once daily, the overall response rate (ORR) was reported to be 67% (95% CI, 51-80). 
• Median time to best response coinciding with the first scheduled response assessment was 12.3 weeks. 
• Patient response was seen for all organs involved with cGVHD, including the skin, mouth, liver, and gastrointestinal tract. 
• Nearly half of the patients (48%) had responses lasting ≥5 months.

iMAGINE (ClinicalTrials.gov Identifier: NCT03790332)

• The safety and efficacy of Imbruvica were evaluated in an open-label, multicenter, single-arm trial for the treatment of pediatric and young adult patients age 1 year to less than 22 years with moderate or severe cGVHD.
• Results showed an ORR (main efficacy outcome measure) of 60% (n=28; 95% CI, 44-74) through week 25, of which 4% (n=2) of patients achieved CR and 55% (n=26) achieved PR. 
• Median duration of response was 5.3 months (95% CI, 2.8-8.8).  
• Median time to first response was 0.9 month (range, 0.9-6.1 months), and the median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI, 4.6-not evaluable).
• 50% of patients 12 years of age and older showed at least a 7-point decrease in patient-reported symptom bother through week 25, as assessed by the Lee Symptom Scale overall summary score.