Modakafusp Alfa for Multiple Myeloma

(iinnovate-2 Trial)

No longer recruiting at 69 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Takeda

Must be taking: Lenalidomide

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Other MM studies, Primary amyloidosis, CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years for Group 1, up to 5 years for Groups 2 and 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called modakafusp alfa for people with multiple myeloma, a type of blood cancer. The main goals are to identify any side effects when combined with other medicines and to determine the safest effective dose. Participants will receive modakafusp alfa through an IV and may be grouped with different combinations of other medications. This trial may suit those with multiple myeloma who have tried other treatments but need additional therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids greater than 10 mg/dL of prednisone or equivalent, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that modakafusp alfa, when combined with other treatments, has a promising safety record. This drug aids the immune system in fighting multiple myeloma, a type of blood cancer, and patients generally tolerate it well.

For instance, studies have tested modakafusp alfa with drugs like lenalidomide, pomalidomide, carfilzomib, bortezomib, or daratumumab, focusing on safety and patient tolerance. The results suggest that side effects are manageable, with no unexpected harmful reactions.

In treating multiple myeloma, this approach targets cancer cells while minimizing side effects. Although the treatment remains in early clinical trials, researchers are primarily working to confirm its safety and determine the best dose. Overall, initial results are encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about modakafusp alfa for multiple myeloma because it offers a new approach compared to existing treatments like lenalidomide, pomalidomide, and carfilzomib. Modakafusp alfa is unique because it is designed as an immunocytokine, a type of treatment that combines an antibody with a cytokine to specifically target and enhance the immune response against cancer cells. This targeted action could potentially lead to improved effectiveness and fewer side effects. Additionally, its administration via intravenous infusion allows for precise control over dosing and timing, which might optimize its therapeutic benefits.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that modakafusp alfa may help treat relapsed or refractory multiple myeloma (RRMM). Studies found that modakafusp alfa, when used alone, helped 32% to 41% of patients. It works by sending a specific signal to myeloma and immune cells, which can kill cancer cells and boost the immune system. This trial studies modakafusp alfa in combination with other drugs like lenalidomide, pomalidomide, carfilzomib, bortezomib, and daratumumab. Researchers are evaluating these combinations to improve effectiveness and determine the best dose, with promising results and general safety observed. ^{3 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with Multiple Myeloma who've had a stem cell transplant within the past 12 months and are MRD positive post-transplant. They should have good organ function, an ECOG status of 0-2, and no progression after initial therapy. Excluded are those in other MM trials, treated with modakafusp alfa before, or with certain medical conditions like severe allergies to trial drugs or active hepatitis B/C or HIV.

Inclusion Criteria

My organ functions are within the required range for the study.

I had a stem cell transplant for multiple myeloma within the last 6 months.

I have not had a bone marrow or organ transplant.

Exclusion Criteria

My heart's electrical cycle is longer than normal.

My multiple myeloma has spread to my brain or meninges.

I haven't had cancer, except for specific low-risk types, in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive modakafusp alfa in combination with other drugs based on their assigned group until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

Up to 2 years for Group 1, up to 5 years for Groups 2 and 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Modakafusp alfa

Trial Overview The study is testing modakafusp alfa combined with other myeloma treatments (Carfilzomib, Lenalidomide etc.) to find the highest safe dose. Participants will receive increasing doses of modakafusp alfa through IV until they reach a dose that's effective without harmful side effects.

How Is the Trial Designed?

Group I: Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide Experimental Treatment 3 Interventions

Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with daratumumab injection subcutaneously on Days 1, 8, 15 and 22 of Cycles 1 and 2, further followed by on Days 1 and 15 of Cycles 3 to 6, thereafter on Day 1 on a 28-day (4-week) treatment cycle along with pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Group II: Group 3 (RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib Experimental Treatment 3 Interventions

Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle along with bortezomib injection subcutaneously on Days 8, 15 and 22 for the first 8 cycles and subsequently on Days 8 and 22 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Group III: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg Experimental Treatment 2 Interventions

Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 4 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.

Group IV: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg Experimental Treatment 2 Interventions

Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 2 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.

Group V: Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 Experimental Treatment 2 Interventions

Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 20/70 milligrams per meter square (mg/m\^2) carfilzomib IV, on Day 1, 8 and 15 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first.

Group VI: Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Bortezomib Experimental Treatment 3 Interventions

Participants were planned to receive modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with bortezomib injection subcutaneously on Days 8, 15, and 22 for the first 8 cycles and subsequently on Days 8 and 22 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Group VII: Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg Experimental Treatment 2 Interventions

Participants received 80 milligrams (mg) modakafusp alfa, infusion intravenously (IV), once on Day 1, once every 4 weeks (Q4W), in combination with 10 mg lenalidomide capsules orally once daily continuously on Days 1 to 28, in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or to a maximum of 2 years for measurable/minimal residual disease-negative (MRD \[-\]) participants, whichever occurred first.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Citations

1. myeloma.org myeloma.org/videos/updated-results-modakafusp-alfa-tak-573-safety-efficacy-phase-12-study-rrmm-patients

Updated Results on Modakafusp Alfa (TAK-573) Safety ... Modakafusp alfa has a novel mechanism of action and has shown encouraging activity with a manageable safety profile in RRMM patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03215030

NCT03215030 | A Study of Modakafusp Alfa on Adult ... The study will determine the safety, tolerability, and efficacy of modakafusp alfa as single agent and in combination with dexamethasone in participants with ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125010171

A phase 2, randomized study of modakafusp alfa as ... The most common treatment-related adverse events (TEAEs) in the 120 and 240 mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%) ...

4. ashpublications.org ashpublications.org/blood/article/146/9/1051/537013/A-phase-2-randomized-study-of-modakafusp-alfa-as-a

A phase 2 randomized study of modakafusp alfa as a single ... This study confirms the efficacy of single-agent modakafusp alfa for patients with RRMM at both recommended phase 2 doses. ORRs were 32% and 41% ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40279508/

A phase 2 randomized study of modakafusp alfa as ... The most common treatment-related adverse events (TEAEs) in the 120- and 240-mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%; ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05556616

NCT05556616 | A Study of Modakafusp Alfa in Adult ... The study will evaluate the safety, tolerability and determine the recommended dose of modakafusp alfa in combination with lenalidomide in participants with ...

7. ashpublications.org ashpublications.org/blood/article/145/9/944/534313/Targeted-interferon-therapy-with-modakafusp-alfa

Targeted interferon therapy with modakafusp alfa for relapsed ... Modakafusp alfa delivers interferon alfa signaling to CD38+ myeloma and immune cells leading to myeloma cell death and immune activation.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11969263/

Targeted interferon therapy with modakafusp alfa for ... Modakafusp alfa delivers interferon alfa signaling to CD38 + myeloma and immune cells leading to myeloma cell death and immune activation.

9. loyolamedicine.org loyolamedicine.org/clinical-research/clinical-trials/NCT03215030

NCT03215030 The main aims of this 3-part study are as follows: Part 1: To determine any side effects from modakafusp alfa single treatment and how often they occur.