Study 1129

The safety and efficacy of IMBRUVICA in cGVHD were evaluated in Study 1129 (NCT02195869), an open-label, multi-center, single-arm trial of 42 patients with cGVHD after failure of first line corticosteroid therapy and requiring additional therapy. IMBRUVICA was administered orally at 420 mg once daily. The responses were assessed by investigators using the 2005 National Institute of Health (NIH) Consensus Panel Response Criteria with two modifications to align with the updated 2014 NIH Consensus Panel Response Criteria.

The median age was 56 years (range, 19 to 74 years), 52% were male, and 93% were White. The most common underlying malignancies leading to transplantation were acute lymphocytic leukemia, acute myeloid leukemia, and CLL. The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was 2 (range, 1 to 3 treatments), and 60% of patients had a Karnofsky performance score of ≤ 80. The majority of patients (88 %) had at least 2 organs involved at baseline, with the most commonly involved organs being mouth (86%), skin (81%), and gastrointestinal tract (33%). The median daily corticosteroid dose (prednisone or prednisone equivalent) at baseline was 0.3 mg/kg/day, and 52% of patients were receiving ongoing immunosuppressants in addition to systemic corticosteroids at baseline. Prophylaxis for infections were managed per institutional guidelines with 79% of patients receiving combinations of sulfonamides and trimethoprim and 64% receiving triazole derivatives.

Efficacy results are shown in Table 30.

The median time to response coinciding with the first scheduled response assessment was 12.3 weeks (range, 4.1 to 42.1 weeks). Responses were seen across all organs involved for cGVHD (skin, mouth, gastrointestinal tract, and liver).

ORR results were supported by exploratory analyses of patient-reported symptom bother which showed at least a 7-point decrease in Lee Symptom Scale overall summary score in 24% (10/42) of patients on at least 2 consecutive visits.

iMAGINE

The safety and efficacy of IMBRUVICA were evaluated in iMAGINE (NCT03790332), an open-label, multi-center, single-arm trial of IMBRUVICA for the treatment of pediatric and young adult patients age 1 year to less than 22 years with moderate or severe cGVHD as defined by NIH Consensus Criteria. The study included 47 patients who required additional therapy after failure of one or more prior lines of systemic therapy. All patients had platelets ≥ 30 x 109/L; absolute neutrophil count ≥ 1.0 x 109/L; AST or ALT ≤ 3 x ULN; total bilirubin of ≤ 1.5 x ULN; and estimated creatinine clearance ≥ 30 mL/min. Patients were excluded if single organ genitourinary involvement was the only manifestation of cGVHD.

Patients age 12 years and older were treated with IMBRUVICA 420 mg orally once daily, and patients age 1 year to less than 12 years were treated with IMBRUVICA 240 mg/m2 orally once daily. Concomitant treatment with supportive care therapies for cGVHD was permitted. Initiation of new systemic cGVHD therapy while on study was not permitted.

The median age was 13 years (range, 1 to 19 years). Of the 47 patients, 70% of patients were male, and 36% were White, 9% were Black or African American, 55% were other or unreported. The median time since cGVHD diagnosis was 16.1 months, the median number of prior cGVHD treatments was 2 (range, 1 to 12). The majority of patients (87%) had at least 2 organs involved at baseline, with lung involvement at baseline in 49% of patients; 26% of patients had a Karnofsky/Lansky performance score of <80\. The median daily corticosteroid dose (prednisone or prednisone equivalent) at baseline was 0.47 mg/kg/day, and 61% (19 of 31) patients were receiving ongoing immunosuppressants in addition to systemic corticosteroids at baseline. Prophylaxis for infections was managed per institutional guidelines, with 72% of patients receiving combinations of sulfonamides and trimethoprim and 70% receiving systemic antifungal agents. 

The efficacy of IMBRUVICA was established based on overall response rate (ORR) through Week 25, where overall response included complete response or partial response according to the 2014 National Institutes of Health (NIH) Consensus Development Project Response Criteria. The efficacy results are shown in Table 31. 

CI = confidence interval; ORR = overall response rate.

a Assessment based on 2014 NIH Consensus Development Project Response Criteria.

b Based on all responders in the study, calculated from first response to progression, death, or new systemic therapies for cGVHD.

The median time to first response was 0.9 month (range, 0.9 to 6.1 months). The median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI: 4.6, not evaluable).

ORR results were supported by exploratory analyses of patient-reported symptom bother which showed at least a 7-point decrease in Lee Symptom Scale overall summary score through Week 25 in 50% (13/26) of patients age 12 years and older.