A Safety and Preliminary Efficacy, Pharmacokinetics, and ImmunogenicityStudy
Research type
Research Study
Full title
A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Modakafusp Alfa (TAK-573) as a Single Agent in Patients With Relapsed Refractory Multiple Myeloma
IRAS ID
1005574
Contact name
Patricia Thomas
Contact email
Sponsor organisation
Takeda Development Center Americas, Inc.
Eudract number
2021-006038-37
Clinicaltrials.gov Identifier
Research summary
Summary of Research
Multiple myeloma (MM) is a cancer which forms in plasma cells (type of white blood cells). Although treatments for MM have improved in the last 10 years, sufferers who become refractory (the cancer is resistant to or has not responded to treatment), still have bleak prognosis.This study will evaluate the safety and tolerability, as well as the anti-myeloma activity, and identify the most appropriate dose and schedule of modakafusp alfa (formerly TAK-573) as a treatment for participants with MM.
The monoclonal antibody (mAb, a lab made protein which binds to targets in the body) modakafusp alfa, is a fusion protein, combining a CD38 antibody with cytokine interferon-alpha (IFN-α) signalling molecules. This combination allows CD38 (a tumour cell surface-expressed antigen that causes the immune system to produce antibodies against) expressing cells, including MM cells, to be targeted. Cytokine interferons, including IFN-α, trigger defence mechanisms, and have previously been shown to have inhibitory effects on some tumours, however toxicity can occur which historically stopped it being used in many patients.
To counter this toxicity, its hoped modakafusp alfa will reduce the binding affinity of IFN-α (KD) to its receptor, interferon alpha receptor. This will reduce the binding of IFN-α to nontargeted, CD38-negative cells, while increasing the concentration of IFN-α on CD38-positive cells, causing the desired on-target IFN pathway activation.
This study is conducted in 2 phases. Phase 1 Part 1 and Phase 2 Part 2 of the study are now complete. Phase 2 of the study, which includes the Part 2 expansion and Part 3 extension where UK participants will be enrolled, also looks at the anti-myeloma activity and safety of modakafusp alfa, in a more robust manner.
There will be about 325 participants taking part in this study at about 80 study clinics across North America, Asia and Europe.
Summary of Results
This summary gives the main results of this single study. Other studies may give different results. Researchers look at the results of many studies to decide which medicines work best and are safest for patients. Always speak with your doctor before changing your treatment.
Part 1
In Part 1 of the treatment period, researchers increased the dose gradually to see how it affected participants. They wanted to find the highest safe dose to be used in the future parts. To do this, they tested the medicine in 4 different schedules. The treatment schedules for the study medicines (Modakafusp alfa) are below:
Researchers wanted to see which of the following schedules were safe and well tolerated by the participants.
Schedule A:
- Once a week for 2 cycles.
- Followed by 1 infusion every 2 weeks in Cycle 3 to 6.
- From Cycle 7, the infusion was given 1 time every 4 weeks.
- Each cycle was 4 weeks long.
Schedule B
- Once every 2 weeks.
- Each cycle was 4 weeks long.Schedule C
- Once every 3 weeks.
- Each cycle was 3 weeks long.Schedule D
- Once every 4 weeks.
- Each cycle was 4 weeks long.Researchers found the maximum dose that participants could tolerate based on DLTs (dose limiting toxicities). At the end of Part 1, researchers chose the dose schedules C and D to use in Part 2.
Part 2
In Part 2, researchers wanted to check how well modakafusp alfa worked when given along with dexamethasone.
Participants randomly received either modakafusp alfa alone or with dexamethasone. Dexamethasone was given once every week.
Throughout these parts, researchers checked vital signs, physical exams, and took blood and urine samples for various tests. Participants took the study medications in every 3- or 4-week cycles until their cancer worsened, they had serious medical problems, they died or left the study.Researchers wanted to learn how safe modakafusp alfa was, how well it was tolerated, and how well it worked in participants with RRMM (Relapsed or Refractory Multiple Myeloma). They answered the following questions:
Part 1 and Japan treatment group
How many participants had medical problems?
Researchers checked if participants had medical problems during Part 1. The following information shows the number of participants with DLTs (dose limiting toxicities), changes in dose, serious medical problems, and those who stopped the study due to medical problems.
Number of Participants With Medical Problems:
Medical problems:
• Schedule A (20 participants): 100%
• Schedule B (8 participants): 100%
• Schedule C (7 participants): 100%
• Schedule D (21 participants): 100%
DLTs (dose limiting toxicities):
• Schedule A (4 participants): 20%
• Schedule B (3 participants): 38%
• Schedule C (0 participants)
• Schedule D (3 participants): 14%
Grade 3 or higher medical problem:
• Schedule A (19 participants): 95%
• Schedule B (8 participants): 100%
• Schedule C (6 participants): 86%
• Schedule D (19 participants): 90%
Serious medical problems:
• Schedule A (8 participants): 40%
• Schedule B (6 participants): 75%
• Schedule C (2 participants): 29%
• Schedule D (13 participants): 62%Discontinued the treatment due to medical problems:
• Schedule A (3 participants): 15%
• Schedule B (2 participants): 25%
• Schedule C (0 participants)
• Schedule D (3 participants): 14%
Modified their dose due to medical problems
• Schedule A (9 participants): 45%
• Schedule B (4 participants): 50%
• Schedule C (4 participants): 57%
• Schedule D (12 participants): 57%• All participants in the Japan treatment group had medical problems. None of the participants had DLTs, and serious medical problems. All the Grade 3 or higher problems were related to blood.
• 1 participant (20%) in the Japan treatment group discontinued the treatment due to medical problems.
• Participants in the Japan treatment group stopped the study early as per the sponsor’s decision and therefore the results did not provide a definite conclusion.PART 2
How did participants respond to the treatment in Part 2?
The results in the table below show the number of participants who responded to treatment in each schedule.
Number of Participants Who Responded to Treatment in Part 2
• Schedule C Modakafusp alfa alone (8 participants): 0
• Schedule C Modakafusp alfa + Dexamethasone (3 participants): 0
• Schedule D Modakafusp alfa alone (25 participants) : 12 Participants (48%)
• Schedule D Modakafusp alfa + Dexamethasone (25 participants): 8 participants (32%)Overall, the results showed that modakafusp alfa was tolerated by the participants in different doses and it worked against multiple myeloma in some participants.
REC name
West of Scotland REC 1
REC reference
22/WS/0079
Date of REC Opinion
13 Jul 2022
REC opinion
Further Information Favourable Opinion