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MagnetisMM-5: An open-label, multicenter, randomized phase 3 study of elranatamab as monotherapy and in combination with daratumumab in patients with relapsed/refractory multiple myeloma.

2022· article· en· W4286294091 on OpenAlexaff
Sebastian Grosicki, Jacob Crafoord, Youngil Koh, Darrel White, Ulf‐Henrik Mellqvist, Eric Leip, Arthur J. Kudla, Gregory Finn, Łukasz Pruchniewski

Bibliographic record

VenueJournal of Clinical Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicMultiple Myeloma Research and Treatments
Canadian institutionsQueen Elizabeth II Health Sciences CentreDalhousie University
FundersPfizer
KeywordsDaratumumabMedicineLenalidomideInternal medicineCombination therapyOncologyClinical endpointPomalidomidePhases of clinical researchMultiple myelomaRegimenDexamethasoneRefractory (planetary science)PharmacologyClinical trial

Abstract

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TPS8074 Background: Elranatamab (PF-06863135) is a humanized bispecific antibody that targets both B cell maturation antigen (BCMA)-expressing multiple myeloma (MM) cells and CD3-expressing T cells, with binding resulting in T cell-mediated cytotoxicity. Elranatamab has demonstrated antitumor activity and delayed tumor progression in preclinical studies, as well as promising efficacy and manageable safety in the ongoing phase 1 MagnetisMM-1 study in patients (pts) with relapsed/refractory MM (Bahlis et al, J Clin Oncol 2021). Methods: MagnetisMM-5 is an open-label, multicenter, randomized phase 3 study designed to evaluate the efficacy and safety of subcutaneous (SC) elranatamab monotherapy and SC elranatamab + SC daratumumab in pts with relapsed/refractory MM who have received prior therapy, including lenalidomide and a proteasome inhibitor (PI). The study consists of 2 parts. In part 1, a minimum of 20 pts will be enrolled to assess the safety of an elranatamab priming regimen and identify the recommended combination dose for SC elranatamab + SC daratumumab for part 2. The primary endpoint of part 1 is dose-limiting toxicities encompassing the elranatamab monotherapy priming duration (14 d) and the first cycle of SC elranatamab + SC daratumumab dosing (28 d). In part 2, ̃450 pts will be stratified by prior lines of therapy (1 vs 2–3 vs ≥4) and prior treatment with anti-CD38 therapy (yes vs no) and enrolled in a 1:1:1 ratio to receive SC elranatamab or SC elranatamab + SC daratumumab or SC daratumumab + oral pomalidomide + oral dexamethasone. The primary endpoint of part 2 is progression-free survival (PFS), according to International Myeloma Working Group (IMWG) response criteria and blinded independent review. Secondary endpoints include PFS and PFS on next-line treatment by investigator per IMWG, overall survival, objective response rate, duration of response, complete response (CR) rate, duration of CR, time to response, overall and sustained minimal residual disease negativity rates, safety, quality of life, immunogenicity, and PK. Key inclusion criteria are age ≥18 y, MM diagnosis with measurable disease according to IMWG criteria, ECOG performance status 0–2, and clinical laboratory values within specified ranges. For part 2, pts should have received ≥1 prior line of anti-myeloma therapy, including treatment with lenalidomide and a PI. Key exclusion criteria include smoldering MM, plasma cell leukemia, amyloidosis, POEMS syndrome, stem cell transplant within 12 wk of enrollment, primary refractory MM, active, uncontrolled bacterial, fungal, or viral infections, previous treatment with BCMA-targeted therapy, anti-CD38 therapy within 6 mo of the first dose of study treatment, and previous pomalidomide therapy. MagnestisMM-5 will include sites in 28 countries. Clinical trial information: NCT05020236.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0010.000
Science and technology studies0.0010.002
Scholarly communication0.0020.002
Open science0.0020.001
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0050.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.077
GPT teacher head0.453
Teacher spread0.376 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations14
Published2022
Admission routes1
Has abstractyes

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