Title
A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study to Determine the Safety and Efficacy of BGB-11417 as Monotherapy, in Combination With Dexamethasone and Carfilzomib/Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14)

Description
Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in combination with dexamethasone and carfilzomib intravenously across two cohorts with a monotherapy component as well.

Objective
Part 1 (Dose Escalation)

Primary Objectives:
-To evaluate the safety and tolerability of BGB-11417 in combination with dexamethasone and dexamethasone plus carfilzomib in patients with relapsed/refractory (R/R) multiple myeloma (MM) and t(11;14)
-To determine the maximum tolerated dose/maximum assessed dose for BGB-11417 in combination with dexamethasone in patients with R/R MM and t(11;14)
-To determine the recommended Phase 2 dose (RP2D) of BGB-11417 in combination with dexamethasone to be used in Part 2 (cohort expansion)
-To determine the recommended doses for the combination of BGB-11417 plus dexamethasone plus carfilzomib to be used in
Part 2

Secondary Objective:
-To assess the pharmacokinetics of BGB-11417 in combination with dexamethasone and with
dexamethasone plus carfilzomib

Part 2 (Cohort Expansion)

Primary Objectives
-To evaluate the safety and tolerability of BGB-11417 at the recommended Phase 2 dose as monotherapy and in combination with dexamethasone in patients with R/R MM and t(11;14)
-To evaluate the safety and tolerability of BGB-11417 in combination with dexamethasone plus carfilzomib at the recommended dose for the combination therapy in patients with R/R MM and t(11;14)
-To evaluate the efficacy of BGB-11417 as monotherapy, in combination with dexamethasone, and with dexamethasone plus carfilzomib in patients with R/R MM and t(11;14) as measured by overall response rate and additional response rates

Secondary Objective
-To evaluate the efficacy of BGB-11417 as monotherapy, in combination with dexamethasone, and with dexamethasone plus carfilzomib in patients with R/R MM and t(11;14) as measured by duration of response, time to response, and time-to-event outcomes

Treatment Experimental: Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD)
Drug: BGB-11417
Administered orally daily
Drug: Dexamethasone
Once weekly either orally or intravenously
Drug: Carfilzomib
Administered intravenously weekly

Experimental: Part 2 Cohort Expansion
There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417
Drug: BGB-11417
Administered orally daily
Drug: Dexamethasone
Once weekly either orally or intravenously
Drug: Carfilzomib
Administered intravenously weekly

Key Eligibility Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)

Measurable disease defined as:


M-spike >/= 500mg/dL, or ii. Urine protein M-spike of >/= 200 mg/day, or iii. Serum free light chains >/= 10 mg/dL, and an abnormal κ:λ ratio


Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy.


Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM.

Refractory MM is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy or progresses within 60 days of last therapy.


Participants in Part 1 should have failed all other available options including having had >/= 3 prior lines of therapy including a proteasome inhibitor, IMiD agent, and an anti-CD38 monoclonal antibody.

Participants in Part 2 should have had and failed >/= 1 but
Note: A line of therapy consists of greater >/= 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens. Induction therapy with consolidation and maintenance following stem cell transplant is considered a single line of therapy.

Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory and not have had carfilzomib within the past 6 months


Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing assay in a pre-defined laboratory


fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing.


Adequate organ function defined as:


Hemoglobin >/= 8.0 g/dL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions

Platelet count >/= 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions

Absolute neutrophil count (ANC) >/= 1000/mm3 [ANC = (% of segmented neutrophils + % of segmented bands) x total WBC count within 7 days before first dose of study treatment

ALT and AST /= 45 mL/min/1.73 m2 calculated by the MDRD-6 formula.

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UW Health University Hospital