Phase 3 SHINE results show postive results for IMBRUVICA (ibrutinib) in Mantle Cell Lymphoma

MCL is a type of aggressive, rare non-Hodgkin lymphoma (NHL) that is incurable and difficult to treat. It commonly affects people over the age of 65, who typically cannot tolerate intensive chemoimmunotherapy and stem cell transplantation, resulting in poor clinical outcomes and contributing to the need to develop additional treatment options for these patients.

"There is an urgent need to improve outcomes for older patients with MCL," said Michael L. Wang, M.D., Professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center and principal study investigator.‡ "Given the median progression-free survival of 6.7 years, the ibrutinib combination demonstrated the potential to be a first-line treatment in this population."

The Phase 3 SHINE (MCL3002) study – sponsored by Janssen Biotech, Inc., in collaboration with Pharmacyclics LLC, an AbbVie Company – enrolled 523 patients aged 65 years or older with newly diagnosed MCL. All participants were randomly assigned to receive IMBRUVICA (560 mg orally daily until progression or unacceptable toxicities) or placebo plus BR for a maximum of six 28-day cycles; participants with a complete response (CR) or partial response (PR) continued to receive maintenance therapy with rituximab every second cycle for a maximum of 12 additional doses. IMBRUVICA or placebo was administered daily until progressive disease or unacceptable toxicity.

The SHINE study met its primary endpoint of progression-free survival (PFS). Key findings from the Phase 3 SHINE study include:

With a median follow-up of 84.7 months, the IMBRUVICA plus BR and rituximab maintenance combination showed a statistically significant and clinically meaningful 2.3-year improvement in median PFS (6.7 years) vs. BR (4.4 years). This is a 50 percent improvement as compared to patients treated with BR and rituximab maintenance (stratified hazard ratio [HR]: 0.75, 95 percent confidence interval [CI], 0.59-0.96; p = 0.011).

Key secondary endpoints included: CR, time-to-next treatment (TTNT), overall survival (OS), and overall response rate (ORR).

• A CR was achieved in 171 patients (65.5 percent) in the IMBRUVICA plus BR arm and 151 patients (57.6 percent) in the placebo arm (p = 0.057). The rates of objective response were similar between the two arms (IMBRUVICA plus BR: 89.7 percent; placebo: 88.5 percent).
• Median TTNT was not reached in the IMBRUVICA plus BR arm, the median TTNT was 92 months in the placebo plus BR arm (p < 0.001).
• OS was similar between treatment arms and median OS was not reached in either treatment arm (p = 0.06).

"More than eight years since its first FDA approval, IMBRUVICA has treated over 250,000 patients globally, fundamentally changing the treatment paradigm for complex B-cell malignancies," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. "The Phase 3 SHINE study reinforces our continued commitment to the development of IMBRUVICA to provide meaningful differences and change outcomes for patients with B-cell malignancies where high unmet medical needs still remain."

The safety profile of the IMBRUVICA plus BR regimen was consistent with known safety profiles of IMBRUVICA as well as BR.

IMBRUVICA is currently approved globally for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Within the U.S., this indication is approved under accelerated approval based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).