A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

Overview

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. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found.

Part 2: To assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. Dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants.

Part 3: To find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa.

Participants will receive modakafusp alfa at one of two doses which will be given through a vein.

SparkCures ID 907
Trial Phase Phase 1/2
Enrollment 336 Patients
Treatments
Tags
Trial Sponsors
  • Takeda Oncology
NCT Identifier

NCT03215030

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

For Parts 1 and 2:

  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • 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).
    • Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD.

For Part 3:

  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • Has previously received at least 3 lines of myeloma therapy.
    • Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. Participants who are primary refractory, meaning they never achieved at least a MR with any previous treatment line, are not eligible.
  • For participants in Part 2 and 3 only: Measurable disease is defined as :
    • Serum M-protein ≥500 mg/dL (≥5 g/L)
    • Urine M-protein ≥200 mg/24 hours.
    • Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
  • During Part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter) detected by physical examination or imaging.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • Has previously received at least 3 lines of myeloma therapy (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).
    • Has either refractory to or intolerant of at least one proteasome inhibitor and a least one immunomodulatory drug.
  • For participants in MTD/OBD cohort expansion and Phase 2 only: participant has measurable disease.
  • During dose escalation only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [>=] 10 percent [%]) and/or plasmacytoma (>=1 centimeter [cm] in diameter) detected by physical examination or imaging.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria:

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 macroglobinemia macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).
  • Has sensory or motor neuropathy of NCI CTCAE >=Grade 3.
  • Who have received autologous stem cell transplant (SCT) 60 days before first infusion of TAK-573 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.
  • Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to ( <= ≤) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to <= ≤ Grade 2 or baseline.
  • Has clinical signs of central nervous system involvement of MM.

For Part 3:

  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded.
  • In addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory MM, current central nervous system involvement of MM, myelodysplastic syndrome, myeloproliferative syndrome, or have had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.

The following criteria is provided for health care professionals.

For Parts 1 and 2:

  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • 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).
    • Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD.

For Part 3:

  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • Has previously received at least 3 lines of myeloma therapy.
    • Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. Participants who are primary refractory, meaning they never achieved at least a MR with any previous treatment line, are not eligible.
  • For participants in Part 2 and 3 only: Measurable disease is defined as :
    • Serum M-protein ≥500 mg/dL (≥5 g/L)
    • Urine M-protein ≥200 mg/24 hours.
    • Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
  • During Part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter) detected by physical examination or imaging.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  • Has MM defined by the IMWG criteria with evidence of disease progression and:
    • In need of additional myeloma therapy as determined by the investigator.
    • Has previously received at least 3 lines of myeloma therapy (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).
    • Has either refractory to or intolerant of at least one proteasome inhibitor and a least one immunomodulatory drug.
  • For participants in MTD/OBD cohort expansion and Phase 2 only: participant has measurable disease.
  • During dose escalation only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [>=] 10 percent [%]) and/or plasmacytoma (>=1 centimeter [cm] in diameter) detected by physical examination or imaging.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria:

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 macroglobinemia macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).
  • Has sensory or motor neuropathy of NCI CTCAE >=Grade 3.
  • Who have received autologous stem cell transplant (SCT) 60 days before first infusion of TAK-573 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.
  • Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to ( <= ≤) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to <= ≤ Grade 2 or baseline.
  • Has clinical signs of central nervous system involvement of MM.

For Part 3:

  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded.
  • In addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory MM, current central nervous system involvement of MM, myelodysplastic syndrome, myeloproliferative syndrome, or have had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Georgia
Verified Winship Cancer Institute of Emory University

SparkCures Verified Accurate, up-to-date information. Learn more

Massachusetts
Nebraska
New Jersey
Verified John Theurer Cancer Center Hackensack Meridian Health

SparkCures Verified Accurate, up-to-date information. Learn more

North Carolina
Ohio
Pennsylvania

Published Results

Modakafusp Alfa (TAK-573), an Immunocytokine, Shows Clinical Activity in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-in-Human Phase 1 Study

December 13, 2021

As of May 2021, 83 pts had been treated across all planned dosing schedules. With Q4W dosing, the MTD was exceeded at the 6 mg/kg dose due to DLTs: a grade 3 infusion reaction and prolonged thrombocytopenia and neutropenia, which delayed the start of cycle 2 by >14 days. In total, 24 pts were treated with 1.5 mg/kg modakafusp alfa Q4W (5 pts during dose escalation and 19 pts in an expansion cohort). Analyses include data from all 24 pts. The median number of prior lines of therapy received was 6 (range 4–16); 21 pts (88%) were refractory to an anti-CD38 mAb, and 20 (83%) were triple class-refractory (to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 mAb). Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 18 pts (75%). The most frequent grade 3–4 TEAEs were neutropenia in 12 pts (50%; grade 4 in 6 [25%]), leukopenia in 9 (38%), decreased lymphocyte count in 9 (38%), anemia in 8 (33%), and thrombocytopenia in 8 (33%; grade 4 in 3 [13%]). One pt (4%) had a grade 3 bleeding event and continues on study treatment; 3 pts (13%) had infections (grade 3 in 2 [8%]); and 8 (33%) had infusion reactions (grade 3 in 1 [4%]). The overall response rate (ORR, ≥partial response [PR]) was 42% (complete response [CR], n=2; very good partial response [VGPR], n=5; PR, n=3), and the clinical benefit rate (ORR + minimal response [MR]) was 54% (MR, n=3). Median progression-free survival was 5.7 months (95% confidence interval [CI], 1.9–not reached [NR]), median time to response was 1.9 months (95% CI, 0.95–NR), and median duration of response was 7.4 months (95% CI, 2.3–NR). Among the 21 anti-CD38 mAb-refractory pts, the ORR was 43%, while among the 4 pts who received an anti-CD38 mAb in their most recent line of therapy prior to enrollment, the ORR was 75% (CR, n=1; VGPR, n=2). Correlative studies show evidence of T-cell and natural killer-cell activation, as well as activation of IFN signaling in CD38+ cells, including upregulation of CD38 expression.

Resources

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