Evidence map›Paper›PMID 40686031›Full record

Trial reportClinical and translational science2025

Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma.

Cheryl Li, Andrew Santulli, Scott Van Wart, Lili Yang, Kaveri Suryanarayan, Sarah F Cook, Xavier Parot, Donald E Mager, Neeraj Gupta

Abstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Clinical and translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Cheryl LiQuantitative Clinical Pharmacology, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts, USA.ORCID 0009-0009-5615-8046
Andrew SantulliEnhanced Pharmacodynamics, LLC, Buffalo, New York, USA.ORCID 0009-0001-0384-9320
Scott Van WartEnhanced Pharmacodynamics, LLC, Buffalo, New York, USA.ORCID 0009-0001-8986-2250
Lili YangTranslational Biomarkers and Bioanalytics, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts, USA.ORCID 0000-0001-8031-6408
Kaveri SuryanarayanClinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts, USA.ORCID 0009-0002-8776-1533
Sarah F CookEnhanced Pharmacodynamics, LLC, Buffalo, New York, USA.ORCID 0000-0001-8612-882X
Xavier ParotClinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts, USA.ORCID 0009-0001-0250-3950
Donald E MagerEnhanced Pharmacodynamics, LLC, Buffalo, New York, USA.ORCID 0000-0002-4848-0440
Neeraj GuptaQuantitative Clinical Pharmacology, Takeda Development Center Americas, Inc. (TDCA), Lexington, Massachusetts, USA.ORCID 0000-0002-5500-5218

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Modakafusp alfa (TAK-573) is a novel, first-in-class fusion protein of a humanized anti-CD38 IgG4 kappa antibody fused to attenuated human interferon alfa-2b. It acts as an agonistic innate immunity enhancer through targeted interferon (IFN) signaling and has been investigated as an immune-oncology therapeutic agent in patients with relapsed/refractory multiple myeloma (RRMM). Population PK analysis and sequential PK-PD analysis of serum M-protein (MP) as a primary marker of tumor burden in RRMM were conducted using dose escalation (Part 1) and dose expansion (Part 2) data from 96 RRMM patients enrolled in the Phase 1/2 iinnovate-1 trial. After exploring various structural PK models with different levels of mechanistic complexity, a Michaelis-Menten approximation model that included an anti-drug antibody (ADA) binding model adequately captured the nonlinear PK of modakafusp alfa and the apparent time-varying impact of ADA on the PK. Body weight was a significant predictor of central volume of distribution (exponent of 0.51) but was not predictive of elimination-related parameters given both catabolic and likely target-mediated elimination processes. Serum MP data from patients evaluable at baseline were adequately characterized using the Claret tumor growth inhibition and drug resistance model, with antitumor drug effect using an E

Indexed as

Antibodies, Monoclonal, HumanizedMultiple MyelomaMyeloma ProteinsNeoplasm Recurrence, LocalRecombinant Fusion ProteinsAdultAgedDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleHumansMaleMiddle AgedModels, BiologicalTreatment OutcomeAntibodies, Monoclonal, Humanizedmultiple myeloma M-proteinsMyeloma ProteinsRecombinant Fusion Proteinsinnate immunity enhancerModakafusp alfaPK‐PD modelingpopulation PKrelapsed or refractory multiple myeloma

Identifiers

PMID40686031
PMCPMC12277654

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.