A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma IINNOVATE-2

What's the purpose of this trial?

The main aims of this study is to test for any side effects from modakafusp alfa in combination therapy and to determine the recommended dose of combination therapy with modakafusp. 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. Participants will be given modakafusp alfa through a vein.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Group 1 (NDMM maintenance: modakafusp alfa/lenalidomide) only must have:
    • NDMM based on standard IMWG diagnostic criteria, have undergone standard of care (SOC) induction therapy including an ASCT, and have achieved a major clinical response.
    • A history of measurable disease documented at time of diagnosis (before induction and ASCT).
    • Undergone ASCT within the 12 months of the start of induction therapy and completed ASCT within 180 days before enrollment. Time to initiation of maintenance therapy: participants may start maintenance therapy as early as 60 days after transplant and up to 180 days after transplant. Consolidation cycles are allowed.
    • Post ASCT MRD positive (10^-5 threshold by local SOC methods or central assessment, if a prior local MRD assessment had not been performed).
    • No prior progression after initial therapy (at any time before starting maintenance). Participants whose induction therapy was changed due to suboptimal response or toxicity will be eligible if they do not meet criteria for progression. In addition, no more than 2 regimens will be allowed before ASCT, excluding dexamethasone alone.
    • No prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
    • Recovered to Grade less than or equal to (<=) 1 autologous stem cell transplant (ASCT) -related toxicities from the reversible effects of ASCT (except for alopecia and amenorrhea).
  • Groups 2 and 3 (RRMM doublets and RRMM triplets) must have:
    • Measurable disease, defined as at least one of the following:
      • Serum M-protein >=0.5 g/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
      • Urine M-protein >=200 mg/24 hours on urine protein electrophoresis (UPEP).
      • Serum free light chain (FLC) assay result with an involved FLC level >=10 mg/dL (>=100 mg/L), provided the serum FLC ratio is abnormal (per IMWG criteria).
    • A confirmed diagnosis of MM according to IMWG criteria with documented disease progression in need of additional therapy as determined by the investigator.
  • For Group 2 RRMM doublet arms only: Participants who have received at least 3 prior lines of antimyeloma therapy, including at least 1 proteasome inhibitor (PI), 1 immunomodulatory (IMiD) and 1 anti-CD38 monoclonal antibody (mAb) drug, or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug regardless of the number of prior line(s) of therapy.
  • For Group 3 RRMM triplet arms only: Participants who have received 1 to 3 prior lines of antimyeloma therapy including at least 1 PI and, 1 IMiD, and who are not refractory to the combination partners.
  • For anti-CD38 arms, forced expiratory volume in 1 second >=50% by pulmonary function testing.
  • For carfilzomib arms, baseline echocardiogram with left ventricular ejection fraction >=50%.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening
  • Has adequate organ function at screening as determined by the laboratory values required for enrollment: Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (or >=1*10^9/L); Platelets >=75,000/mm^3 (>=75*10^9/L); Hemoglobin >=8.0 g/dL; estimated creatinine clearance >=30 mL/min (Cockcroft-Gault formula); Total serum bilirubin <=2.0*Upper limit of normal (ULN); an exception for participants with Gilbert's syndrome may be granted after discussion with the sponsor; Liver transaminases (alanine aminotransferase [ALT])/aspartate aminotransferase [AST]) <=3.0*ULN.
  • Has recovered from adverse reactions to prior myeloma treatment or procedures (example, chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Version 5.0 Grade <=1 or baseline treatment or have the toxicity established as sequela, except for sensory or motor neuropathy, which should have recovered to Grade <=2 or baseline; Grade 1 for bortezomib arm.

Exclusion criteria:

  • Currently participating in another MM interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) throughout the duration of this study.
  • Received previous treatment with modakafusp alfa.
  • Has a diagnosis of primary amyloidosis, Waldenström disease, monoclonal gammopathy of undetermined significance or smoldering MM per IMWG criteria or standard diagnostic criteria, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), lymphoplasmacytic lymphoma.
  • Has had another 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 and that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.
  • Has evidence of CNS involvement and/or meningeal involvement due to MM exhibited during screening.
  • Has a 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.
  • Is 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 and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and, a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
  • Has a known history of seropositivity for HIV.
  • Is seropositive for hepatitis C (anti-hepatitis C virus antibody positive or anti-hepatitis C virus-RNA quantitation positive). Exception: Participants with a sustained virologic response with undetectable HCV RNA level at least 12 weeks after completion of antiviral therapy.
  • For bortezomib arms: participants received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization.
  • The participant has a 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.
  • Has QT interval corrected with Fridericia correction method (QTcF) >480 millisecond (ms) (Grade >=2).

Additional Trial Information

Phase 1

Enrollment: 120 patients (estimated)

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


Mayo Clinic (Arizona)

Phoenix, AZ

Not Yet Accepting


University of California Davis Comprehensive Cancer Center

Sacramento, CA

Open and Accepting

Scripps Green Hospital

San Diego, CA

Open and Accepting


University of Colorado Cancer Center Anschutz Cancer Pavilion

Aurora, CO

Not Yet Accepting

Rocky Mountain Cancer Centers (Aurora) Aurora

Aurora, CO

Not Yet Accepting


GBMC Cancer Center - Berman Cancer Institute

Baltimore, MD

Open and Accepting


Dana-Farber Cancer Institute (Main)

Boston, MA

Not Yet Accepting


Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, MI

Not Yet Accepting


Mayo Clinic (Rochester)

Rochester, MN

Not Yet Accepting


Comprehensive Cancer Centers of Nevada (Central Valley)

Las Vegas, NV

Open and Accepting

New York

NYU Langone - Long Island

Mineola, NY

Open and Accepting

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting


Gabrail Cancer Center Research

Canton, OH

Open and Accepting


Vanderbilt-Ingram Cancer Center Henry-Joyce Cancer Clinic

Nashville, TN

Not Yet Accepting


MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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