Clinical trial NCT03984097: A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM)
Official title: An Open-Label, Multicenter Phase 1b Study Investigating the Safety of TAK-079 in Combination With Backbone Regimens for the Treatment of Patients With Newly Diagnosed Multiple Myeloma and for Whom Stem Cell Transplantation Is Not Planned as Initial Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Drug Therapy
TAK-079
CD38
Monoclonal Antibody
Lenalidomide
Bortezomib
Pomalidomide
Velcade
Stem Cell Transplant
Neoplasms, Plasma Cell
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-06-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this original study is to determine the recommended phase 2 dose (RP2D) of TAK-079 when administered to participants with NDMM in combination with the backbone treatment regimen. The purpose of the safety/access cohort is to provide continued access to TAK-079 to participants previously enrolled to a TAK-079 parent study and to evaluate the long-term safety profile of TAK-079.

Detailed description: Treatment phase drug being tested in this study is called TAK-079. TAK-079 is being tested to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) when added to 1 of 2 standard backbone regimens (LenDex or VRd) with newly diagnosed NDMM for whom stem cell transplantation (SCT) is not planned as initial therapy.

The study will enroll approximately 36 participants. Participants will be non-randomly assigned to one of the two treatment groups in the original study or Treatment Phase:

* TAK-079 and LenDex
* TAK-079 and VRd

All enrolled participants will have the opportunity to complete the treatment therapy and then enter the Extension study for as long as participants continue to derive benefit. Safety Extension Phase participants who have previously received and tolerated TAK-079-based parent study will continue to the extension study. The study will also evaluate the long-term safety profile of TAK-079. Participants will continue to receive TAK-079 and, if applicable, SOC backbone therapy as per the parent study.

Eligibility criteria: Inclusion (Inc) Criteria:

1. Must have previously untreated multiple myeloma (MM) as defined by the IMWG criteria requiring treatment according to the investigator.
2. Are appropriate candidates for either the VRd or Rd backbone antimyeloma therapy according to the investigator.
3. Must have measurable disease defined by at least 1 of the following:

   * Serum M-protein \>=1 gram per deciliter (g/dL) (\>=10 gram/liter \[g/L\]).
   * Urine M-protein \>=200 mg/24 hours.
   * Serum FLC assay: involved FLC level \>=10 mg/dL (\>=100 milligram per liter \[mg/L\]) provided the serum FLC ratio is abnormal.
4. Participants receiving lenalidomide must be able to take concurrent prophylactic anticoagulation per standard clinical practice as directed by the investigator.
5. Life expectancy \>3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (\<=) 2.

Inc Criteria for Participants in the Safety/Access Cohort (only):

Participants previously treated with TAK-079 therapy in a Takeda-sponsored TAK-079 parent study. Participants will be eligible to enter this cohort when:

1. The parent study is closed, planned to be closed, or has met its primary objectives.

Exclusion (Exc) Criteria:

1. Prior systemic therapy for MM.

   o treatment with bisphosphonates or a single course of glucocorticoids does not disqualify the participant (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg \[for example, 40 milligram per day (mg/d) for 4 days\] of dexamethasone).
2. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device) within 4 weeks of the first dose of TAK-079 or any agent in the backbone regimen and throughout the duration of this trial.
3. Prior radiation therapy within 14 days of the first dose of TAK-079 or any backbone regimen agents.

   NOTE: Prophylactic localized ("spot") radiation for areas of pain is allowed.
4. Major surgery within 4 weeks before Cycle 1 Day 1 (kyphoplasty is not considered major surgery). Participants should be fully recovered from any surgically related complications.
5. Plasmapheresis within 28 days of randomization.
6. If plasmacytoma is the only measurable parameter for assessing disease response, participant is not eligible because of difficult response evaluation.
7. Clinical signs of meningeal involvement of MM exhibited during screening.
8. Serum positive for human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
9. Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the TAK-079 formulation or agents in the backbone regimen (lenalidomide, bortezomib, dexamethasone) as per the respective prescribing information or for TAK-079, as outlined in the current investigator's brochure (IB).
10. Systemic infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of TAK-079 or any agent in the backbone regimen. Urinary tract infection is not considered a systemic infection.
11. A 12-lead electrocardiogram (ECG) showing a QT interval corrected by Frederica's formula (QTcF) \>470 milliseconds. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG.
12. Diagnosis of primary amyloidosis, Waldenstrom's disease, monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) per IMWG criteria or standard diagnostic criteria, plasma cell leukemia (according to the World Health Organization \[WHO\] criterion: \>=20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 \*10\^9/L), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS syndrome), myelodysplastic syndrome, or myeloproliferative syndrome.
13. History of myelodysplastic syndrome or another malignancy other than MM, except for the following: any malignancy that has been in complete remission for 2 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer (Gleason score \<=6 without known metastatic disease and with no requirement for therapy, or requiring only hormonal therapy and stable prostate-specific antigen for \>=1 year before initiation of study therapy), breast carcinoma in situ with full surgical resection, and treated medullary or papillary thyroid cancer.

Exc Criteria for Participants in the Safety/Access Cohort

1. Participants meeting any of the criteria for treatment discontinuation in the parent study.

Primary outcomes:
measure: Treatment Phase: RP2D of TAK-079
timeFrame: Up to Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Safety Extension Phase: Number of Participants Reporting one or More Serious Adverse Events (SAEs)
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 4 years)
measure: Safety Extension Phase: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 4 years)
measure: Safety Extension Phase: Number of Participants Who Require Dose Modification
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 4 years)
measure: Safety Extension Phase: Number of Participants With TEAEs Leading to Treatment Discontinuation
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 4 years)
Secondary outcomes:
measure: Treatment Phase: Overall Response Rate (ORR)
timeFrame: Up to 2 years
measure: Treatment Phase: Number of Participants Reporting one or More TEAEs and SAEs
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 2 years)
measure: Treatment Phase: Number of Participants With Grade 3 or Higher TEAEs
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 2 years)
measure: Treatment Phase: Number of Participants with TEAEs Leading to Treatment Discontinuation
timeFrame: From first dose up to 30 days after the last dose of study drug (up to 2 years)
measure: Treatment Phase: Number of Participants With AEs Leading to On-study Deaths
timeFrame: From screening up to 30 days after the last dose of study drug (up to 2 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Monterey
country: United States
facility: Pacific Cancer Care
state: California
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: