What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, particularly those involving targeted therapies like monoclonal antibodies (e.g., daratumumab, elotuzumab) and proteasome inhibitors (e.g., bortezomib, carfilzomib), often present side effects such as infections, fatigue, gastrointestinal issues (diarrhea, constipation), neuropathy, and hematologic toxicities (anemia, thrombocytopenia). Specific adverse events can include hypertension, cardiac events, and renal impairment. These side effects vary in frequency and severity depending on the specific drug and combination regimen used.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Multiple Myeloma. Notable drugs include bortezomib, a proteasome inhibitor; lenalidomide, an immunomodulatory drug; and daratumumab, an anti-CD38 monoclonal antibody. These drugs are often used in combination with dexamethasone, a corticosteroid, to enhance their efficacy. Carfilzomib, another proteasome inhibitor, has also been approved for relapsed or refractory Multiple Myeloma. These treatments have shown significant clinical activity and are similar in approach to the targeted therapy being studied with Modakafusp Alfa.

What other types of research exist?

Promising novel alternatives to Modakafusp Alfa for Multiple Myeloma patients include second-generation proteasome inhibitors such as carfilzomib, marizomib, and MLN9708. These agents have demonstrated positive results in clinical trials for relapsed/refractory multiple myeloma.

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CAR T-cell Therapy

Modakafusp Alfa for Multiple Myeloma (iinnovate-1 Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Millennium Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

For Parts 1 and 2: Has previously received at least 3 lines of myeloma therapy (for example, containing an Immunomodulatory imide drug [IMiD], a proteasome inhibitor [PI], an alkylating agent, and/or an anti-CD38 as single agents or in combination)

For Parts 1 and 2: Is either refractory to or intolerant of at least 1 PI and at least 1 IMiD

Must not have

For Parts 1 and 2: Who have received autologous stem cell transplant (SCT) 60 days before first infusion of modakafusp alfa or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression

For Parts 1 and 2: Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 90 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug called modakafusp alfa, given alone or with dexamethasone, for patients whose multiple myeloma has returned or resisted other treatments. The study aims to find the safest and most effective dose while monitoring side effects and benefits. The drug works by specifically targeting cancer cells.

Who is the study for?

This trial is for adults with relapsed/refractory Multiple Myeloma who've had at least 3 prior treatments, including an IMiD and a PI. They must show disease progression needing further therapy and have measurable disease markers. Exclusions include hepatitis B or C infection, central nervous system MM involvement, certain other cancers within the last 3 years, or recent stem cell transplants.

What is being tested?

The study tests Modakafusp alfa's safety and optimal dosing alone or with Dexamethasone in three parts: finding a safe dose without harmful side effects; assessing its effectiveness alone or with standard-dose Dexamethasone; determining the best dose considering risks and benefits. It's administered intravenously at two different doses.

What are the potential side effects?

Potential side effects of Modakafusp alfa may include reactions related to infusion into the vein, immune system complications affecting various organs, fatigue, blood disorders like anemia or clotting issues, as well as increased susceptibility to infections.

Eligibility Criteria

Inclusion Criteria

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

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I have had at least 3 different treatments for myeloma.

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I have not responded to or cannot tolerate at least one proteasome inhibitor and one immunomodulatory drug.

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My condition worsened despite treatments with specific cancer drugs.

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I have undergone at least 3 different treatments for myeloma.

Exclusion Criteria

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

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I had a stem cell transplant and no ongoing immune system treatment for graft disease.

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I have a specific blood or bone marrow condition like POEMS syndrome or Waldenstrom macroglobulinemia.

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My multiple myeloma has affected my brain or spinal cord.

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I don't have certain blood disorders or another cancer besides MM in the last 3 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 90 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 90 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 90 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs

Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs)

Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)

+6 more

Secondary study objectives

Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events

Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa

Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa

+26 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Group I: Part 3 (Dose Extension): Modakafusp alfa 240 mgExperimental Treatment1 Intervention

Participants will receive modakafusp alfa 240 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group II: Part 3 (Dose Extension): Modakafusp alfa 120 mgExperimental Treatment1 Intervention

Participants will receive modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.

Group III: Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mgExperimental Treatment2 Interventions

Dose(s) for Phase 2 will be based on safety and tolerability results from the preceding Phase 1 dose escalation cohorts. Participants in Phase 2 cohorts will receive modakafusp alfa TBD as a single agent. Participants in at least 1 cohort will receive modakafusp alfa TBD and modakafusp alfa TBD and dexamethasone 40 mg, orally, once weekly of each 28-day treatment cycle until treatment discontinuation.

Group IV: Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBDExperimental Treatment1 Intervention

Modakafusp alfa TBD, infusion, IV, once every 4 weeks (Q4W) on Day 1 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

Group V: Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBDExperimental Treatment1 Intervention

Modakafusp alfa TBD, infusion, IV, once every 3 weeks (Q3W) on Day 1 of each 21-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

Group VI: Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBDExperimental Treatment1 Intervention

Modakafusp alfa TBD, infusion, IV, once every 2 weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information.

Group VII: Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kgExperimental Treatment1 Intervention

Modakafusp alfa 0.001 up to 14 milligram per kilogram (mg/kg), infusion, intravenously (IV), once every week (Q1W) on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once on Day 1 of each 28-day treatment cycle until treatment discontinuation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Modakafusp alfa

2022

Completed Phase 2

~290

Dexamethasone

2007

Completed Phase 4

~2650

0 / 8Eligibility 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 targeted therapies such as monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs. Monoclonal antibodies, like daratumumab and isatuximab, target specific proteins on the surface of myeloma cells, leading to their destruction. Proteasome inhibitors, such as bortezomib and carfilzomib, block the proteasome's function, causing an accumulation of proteins within the cell that leads to cell death. Immunomodulatory drugs, like lenalidomide and pomalidomide, enhance the immune system's ability to attack myeloma cells and inhibit their growth. These mechanisms are vital for Multiple Myeloma patients as they offer targeted approaches that can improve treatment efficacy and reduce side effects compared to traditional chemotherapy.

Merkel cell carcinoma: a review.Pomalidomide therapy for myeloma.Emerging drugs in multiple myeloma.