Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma
Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma
The primary objectives of this study included the following:

 Phase 1b:

 -  To establish the maximum tolerated dose (MTD) of oprozomib given in combination with
 lenalidomide and dexamethasone (ORd) or with cyclophosphamide and dexamethasone (OCyd)

 -  To evaluate the safety and tolerability of oprozomib and dexamethasone administered in
 combination with lenalidomide or oral cyclophosphamide

 Phase 2:

 -  To estimate the antitumor activity of each combination regimen, as measured by overall
 response rate (ORR) and complete response rate (CRR)

 -  To evaluate the safety and tolerability of each combination regimens, as assessed by the
 type, incidence, severity and seriousness of adverse events, and abnormalities in
 selected laboratory analytes
Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each
 combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3
 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was
 observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and
 dexamethasone were to remain fixed in all dose cohorts.

 The phase 2 portion of the study was to include up to 35 additional participants in each of
 the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that
 was identified during the phase 1b portion of the study in order to better characterize
 safety and tolerability, and antimyeloma activity.

 This study was stopped by sponsor decision during the dose escalation in phase 1b prior to
 initiation of phase 2.
Key Inclusion Criteria:

 -  Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated
 per the National Comprehensive Cancer Network (NCCN) guidelines, and for whom a
 hematopoietic stem cell transplant is not planned or scheduled during the study or are
 considered ineligible for hematopoietic stem cell transplant, with measurable disease

 -  Creatinine clearance of ≥ 50 mL/min (measured or calculated using the Cockcroft and
 Gault formula)

 Key Exclusion Criteria:

 -  Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a
 total dose of 160 mg or equivalent within 14 days prior to the first dose of study
 treatment). Use of topical or inhaled steroids is acceptable

 -  Radiation therapy within 2 weeks prior to first dose

 -  Major surgery within 3 weeks prior to first dose

 -  Active infection requiring systemic antibiotics, antivirals, or antifungals within 2
 weeks prior to first dose

 -  Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1
 (C1D1) first dose

 -  Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of first
 dose

 -  Other malignancy within the past 3 years except those considered cured by surgical
 resection including some cases of: with the exception of adequately treated basal or
 squamous cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer,
 carcinoma in situ of the breast or cervix, carcinoma in situ of the breast, prostate
 cancer with Gleason Score 6 or less with stable prostate specific antigen levels, or
 cancer considered cured by surgical resection