Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma

A Multicenter, Randomized, Open-label Phase 2 Study Evaluating the Safety and Efficacy of Three Different Regimens of Oral Panobinostat in Combination With Subcutaneous Bortezomib and Oral Dexamethasone in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma Who Have Been Previously Exposed to Immunomodulatory Agents

Note: The study data was transferred to zr pharma& following the divestment of panobinostat to pharma&. Prior to study completion under the sponsorship of Secura Bio, the study was initiated and conducted in part under the sponsorship of Novartis.

The purpose of this study is to investigate the safety and efficacy of 3 different regimens of panobinostat (20 milligrams [mg] thrice a week [TIW], 20 mg twice a week [BIW], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants > 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression.

Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons.

Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks.

All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.

Inclusion Criteria:

• multiple myeloma per International Myeloma Working Group 2014 definition
• requiring treatment for relapsed or relapsed/refractory disease
• measurable disease based on central protein assessment
• received 1 to 4 prior lines of therapy
• prior immunomodulatory agent(s) exposure
• acceptable lab values prior to randomization

Exclusion Criteria:

• primary refractory myeloma
• refractory to bortezomib
• concomitant anti-cancer therapy (other than bortezomib/dexamethasone and bisphosphonates)
• prior treatment with pan-deacetylase inhibitors
• clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
• unresolved diarrhea ≥ Common Terminology Criteria for adverse events grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome and inflammatory bowel disease)

Other protocol-defined inclusion/exclusion criteria may apply.