What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as bortezomib, dexamethasone, cyclophosphamide, lenalidomide, and daratumumab, have a range of side effects. Bortezomib can cause peripheral neuropathy, cytopenias, gastrointestinal distress, and fatigue. Dexamethasone is associated with hyperglycemia, insomnia, and increased infection risk. Cyclophosphamide may lead to cytopenias, infections, and gastrointestinal issues. Lenalidomide's side effects include cytopenias, fatigue, and increased risk of thromboembolic events. Daratumumab can cause infusion-related reactions, respiratory infections, and fatigue. These side effects are important considerations when determining the safety and tolerability of combination therapies in Multiple Myeloma treatment.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Myeloma, often used in combination therapies. Notable approvals include bortezomib, lenalidomide, and dexamethasone, which are frequently used together or with other agents like cyclophosphamide and melphalan. Daratumumab, a monoclonal antibody, has also been approved for use in combination with these drugs. Additionally, ixazomib has been approved for maintenance therapy. These treatments have undergone rigorous clinical trials to establish their safety and efficacy, similar to the dose-escalation studies being conducted for modakafusp alfa.

What other types of research exist?

Promising novel alternatives to Modakafusp Alfa for Multiple Myeloma patients include: 1) CAR T-cell therapies such as idecabtagene vicleucel and ciltacabtagene autoleucel, which have shown significant efficacy in relapsed or refractory multiple myeloma. 2) Bispecific antibodies like teclistamab, targeting BCMA and CD3, which have demonstrated encouraging results in clinical trials. 3) Antibody-drug conjugates such as belantamab mafodotin, which targets BCMA and has been approved for patients with relapsed or refractory multiple myeloma. These therapies represent cutting-edge advancements and offer new hope for patients with multiple myeloma.

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Immunotherapy

Modakafusp Alfa for Multiple Myeloma (iinnovate-2 Trial)

Phase 1

Waitlist Available

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No prior allogeneic hematopoietic stem cell transplant or solid organ transplant

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening

Must not have

Chronic condition requiring the use of systemic corticosteroids >10 mg/dL of prednisone or equivalent, in addition to any required corticosteroids for the treatment of MM

Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the modakafusp alfa formulation or to the study combination agents, the study medications, their analogs, or excipients in the various formulations of any agent per the prescribing information

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called modakafusp alfa, given with other medications, to treat patients with multiple myeloma. The goal is to find the safest and most effective dose. The study focuses on patients who need ongoing treatment or have not responded to previous treatments.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to infusion such as fever or chills, allergic responses to components in the drug mixtures used including skin rashes or breathing difficulties, and general symptoms like fatigue. Organ inflammation could also occur.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have not had a bone marrow or organ transplant.

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I am able to care for myself and perform daily activities.

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I have multiple myeloma as diagnosed by standard criteria.

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My cancer is still detectable after stem cell transplant.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I take more than 10 mg/dL of prednisone or equivalent for a chronic condition, not including my MM treatment.

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I am not allergic to any ingredients in the medication or its similar drugs.

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My heart's electrical cycle is longer than normal.

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My multiple myeloma has spread to my brain or meninges.

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I have been diagnosed with a specific blood or bone marrow condition.

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I have been treated with modakafusp alfa before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Dose-limiting Toxicities (DLTs)

Secondary study objectives

Duration of Response (DOR)

Group 1: Duration of MRD Negativity Status at a Threshold of 10^-5 in Participants Achieving MRD Negativity

Group 1: Percentage of Participants with MRD Negativity Status at a Threshold of 10^-5

+11 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + PomalidomideExperimental Treatment3 Interventions

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 + BortezomibExperimental Treatment3 Interventions

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) Arm 4: Modakafusp alfa + CarfilzomibExperimental Treatment2 Interventions

Modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 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 is met, whichever occurs first. This arm is closed for enrollment after 3 participants were enrolled.

Group IV: Group 2 (RRMM Doublets) Arm 3: Modakafusp alfa + BortezomibExperimental Treatment2 Interventions

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 V: Group 2 (RRMM Doublets) Arm 2: Modakafusp alfa + PomalidomideExperimental Treatment2 Interventions

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 until disease progression, unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Group VI: Group 1 (MM Maintenance) Arm 1: Modakafusp alfa + LenalidomideExperimental Treatment2 Interventions

Modakafusp alfa, infusion intravenously (IV), once on Day 1, once every 4 weeks (Q4W), in combination with 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 MRD \[-\] negative participants, whichever occurs first. Participants who remain MRD positive with demonstrated clinical benefit after 2 years of maintenance therapy may continue treatment beyond 2 years with agreement of the sponsor/designee.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pomalidomide

2011

Completed Phase 2

~1020

Modakafusp alfa

2022

Completed Phase 1

~20

Lenalidomide

2005

Completed Phase 3

~2240

Bortezomib

2005

Completed Phase 3

~1410

Carfilzomib

2017

Completed Phase 3

~1430

Daratumumab

2014

Completed Phase 3

~2000

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Myeloma include monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs. Monoclonal antibodies, such as daratumumab, target specific proteins on the surface of myeloma cells, marking them for destruction by the immune system. Proteasome inhibitors, like bortezomib, block the proteasome's function, leading to the accumulation of toxic proteins within cancer cells, causing cell death. Immunomodulatory drugs, such as lenalidomide, enhance the immune system's ability to fight cancer and inhibit the growth of myeloma cells. These mechanisms are crucial as they target the cancer cells directly or enhance the body's natural defenses, offering multiple pathways to control and potentially eradicate the disease.

The importance of dose and schedule in cancer chemotherapy: epithelial ovarian cancer.Sorafenib for the treatment of multiple myeloma.