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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05590377




Registration number
NCT05590377
Ethics application status
Date submitted
19/10/2022
Date registered
21/10/2022

Titles & IDs
Public title
A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma
Scientific title
A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2022-002169-14
Secondary ID [2] 0 0
TAK-573-2001
Universal Trial Number (UTN)
Trial acronym
iinnovate-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Modakafusp Alfa
Treatment: Drugs - Daratumumab

Experimental: Phase 1 Dose Escalation - Modakafusp alfa 60 to 240 mg, infusion, intravenously, once every 4 weeks (Q4W) with daratumumab 1800 mg, subcutaneously (SC), once weekly (QW) in Cycles 1 and 2, twice weekly (Q2W) in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Experimental: Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab - Modakafusp alfa at dose level 1 (DL1) \[selected from Phase 1 Dose Escalation\] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Experimental: Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab - Modakafusp alfa at dose level 2 (DL2) \[selected from Phase 1 Dose Escalation\] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.


Treatment: Drugs: Modakafusp Alfa
Modakafusp alfa intravenous infusion

Treatment: Drugs: Daratumumab
Daratumumab SC injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants with Dose Limiting Toxicities (DLT)
Timepoint [1] 0 0
Cycle 1 (cycle length=28 days)
Primary outcome [2] 0 0
Phase 1: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Per Severity
Timepoint [2] 0 0
Up to 60 months
Primary outcome [3] 0 0
Phase 2a: Overall Response Rate (ORR)
Timepoint [3] 0 0
Up to 60 months
Secondary outcome [1] 0 0
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Modakafusp Alfa
Timepoint [1] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [2] 0 0
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Modakafusp Alfa
Timepoint [2] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [3] 0 0
Phase 1: AUC8: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Timepoint [3] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [4] 0 0
Phase 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration
Timepoint [4] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [5] 0 0
Phase 1: Apparent Serum Terminal Disposition Rate Constant for Modakafusp Alfa
Timepoint [5] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [6] 0 0
Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa
Timepoint [6] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [7] 0 0
Phase 1: Total Clearance After Intravenous Administration for Modakafusp Alfa
Timepoint [7] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [8] 0 0
Phase 1: Volume of Distribution at Steady State After Intravenous Administration for Modakafusp Alfa
Timepoint [8] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [9] 0 0
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Daratumumab
Timepoint [9] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [10] 0 0
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab
Timepoint [10] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [11] 0 0
Phase 1: Ctrough: Single-Dose and Multiple-dose Observed Concentration at the End of a Dosing Interval for Daratumumab
Timepoint [11] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [12] 0 0
Phase 1: AUC8: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Daratumumab
Timepoint [12] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [13] 0 0
Phase 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration for Daratumumab
Timepoint [13] 0 0
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days)
Secondary outcome [14] 0 0
Phase 1: Overall Response Rate (ORR)
Timepoint [14] 0 0
Up to 60 months
Secondary outcome [15] 0 0
Phase 1 and Phase 2a: Duration of Response (DOR)
Timepoint [15] 0 0
Up to 60 months
Secondary outcome [16] 0 0
Phase 1 and Phase 2a: Progression Free Survival (PFS)
Timepoint [16] 0 0
up to 60 months
Secondary outcome [17] 0 0
Phase 1 and Phase 2a: Overall Survival (OS)
Timepoint [17] 0 0
Up to 60 months
Secondary outcome [18] 0 0
Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies
Timepoint [18] 0 0
Up to 60 months
Secondary outcome [19] 0 0
Phase 1 and Phase 2a: Titer of Anti-drug Antibodies
Timepoint [19] 0 0
Up to 60 months
Secondary outcome [20] 0 0
Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug
Timepoint [20] 0 0
Up to 60 months
Secondary outcome [21] 0 0
Phase 1 and Phase 2a: Rate of Measurable [Minimal] Residual Disease Negative (MRD[-]) Complete Response (CR)
Timepoint [21] 0 0
Up to 60 months
Secondary outcome [22] 0 0
Phase 1 and Phase 2a: Duration of Measurable [Minimal] Residual Disease (MRD) Negativity
Timepoint [22] 0 0
Up to 60 months
Secondary outcome [23] 0 0
Phase 2a: Clinical Benefit Rate (CBR)
Timepoint [23] 0 0
Up to 60 months
Secondary outcome [24] 0 0
Phase 2a: Duration of Clinical Benefit (DCB)
Timepoint [24] 0 0
Up to 60 months
Secondary outcome [25] 0 0
Phase 2a: Disease Control Rate (DCR)
Timepoint [25] 0 0
Up to 60 months
Secondary outcome [26] 0 0
Phase 2a: Duration of Disease Control
Timepoint [26] 0 0
Up to 60 months
Secondary outcome [27] 0 0
Phase 2a: Time to Progression (TTP)
Timepoint [27] 0 0
Up to 60 months
Secondary outcome [28] 0 0
Phase 2a: Time to Response (TTR)
Timepoint [28] 0 0
Up to 60 months
Secondary outcome [29] 0 0
Phase 2a: Time to Next Treatment (TTNT)
Timepoint [29] 0 0
Up to 60 months
Secondary outcome [30] 0 0
Phase 2a: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Per Severity
Timepoint [30] 0 0
Up to 60 months

Eligibility
Key inclusion criteria
1. Documented multiple myeloma (MM) diagnosis per IMWG criteria.
2. Measurable disease, defined as at least 1 of the following:

1. Serum M protein =0.5 grams per deciliter [g/dL] (=5 g/L) on serum protein electrophoresis (SPEP).
2. Urine M protein =200 mg/24 hours on urine protein electrophoresis (UPEP).
3. Serum free light chain (FLC) assay with involved FLC level =10 mg/dL (=100 mg/L) provided serum FLC ratio is abnormal.
3. For participants in the Phase 1 Dose Escalation only:

Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy.
4. For participants in Phase 2a Dose Finding only:

1. Received 1 to 3 prior line(s) of antimyeloma therapy.
2. Must be refractory to prior lenalidomide treatment.
3. Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment.
4. Documented progressive disease on or after the last regimen.
5. Participants must have PR or better to at least 1 line of prior therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior exposure to modakafusp alfa.
2. Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
3. Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade =1 or baseline, except for alopecia.
4. Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
5. Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
6. Participant has congestive heart failure (New York Heart Association Grade =II), cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension.
7. Participant has QT interval corrected by the Fridericia method >480 milliseconds [msec] (Grade =2).
8. Participant has a chronic condition that will require the chronic use of systemic corticosteroids >10 milligrams per day (mg/d) of prednisone or equivalent on top of any required corticosteroids for multiple myeloma (MM).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
China
State/province [14] 0 0
Guangdong
Country [15] 0 0
China
State/province [15] 0 0
Hubei
Country [16] 0 0
China
State/province [16] 0 0
Tianjin
Country [17] 0 0
China
State/province [17] 0 0
Zhejiang
Country [18] 0 0
France
State/province [18] 0 0
Hauts-de-France
Country [19] 0 0
France
State/province [19] 0 0
Provence-Alpes-Cote d'Azur
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Jeollanam-do
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.