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inMIND: A phase 3 study of tafasitamab plus lenalidomide and rituximab versus placebo plus lenalidomide and rituximab for relapsed/refractory follicular or marginal zone lymphoma.

2022· article· en· W4281678979 on OpenAlexaff
Laurie H. Sehn, Kai Hübel, Stefano Luminari, Antonio Salar, Björn E. Wahlin, Ajay K. Gopal, Christophe Bonnet, Shankara Paneesha, Marek Trněný, Hafsat Umar Mashegu, Christine Lihou, Di Li, Christian W. Scholz

Bibliographic record

VenueJournal of Clinical Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsSpinal Cord Injury BCUniversity of British Columbia
Fundersnot available
KeywordsMedicineRituximabLenalidomideFollicular lymphomaInternal medicinePhases of clinical researchOncologyCD20LymphomaClinical trialGastroenterologyMultiple myeloma

Abstract

fetched live from OpenAlex

TPS7583 Background: Most patients with the indolent non-Hodgkin lymphoma (NHL) subtypes follicular (FL) or marginal zone (MZL) respond to first-line treatment but relapse is common, and there is no single standard treatment for patients (pts) with relapsed/refractory (R/R) FL or MZL. Tafasitamab (TAFA) is an Fc-engineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B-cell proliferation via B-cell receptor signaling. In preclinical studies, TAFA has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). Monotherapy with TAFA has shown promising clinical activity in a phase 2a study in pts with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in pts with FL and 33% (n/N = 3/9) in pts with MZL. In an ongoing phase 2, single-arm study (L-MIND, NCT02399085), TAFA + LEN followed by TAFA alone demonstrated an ORR of 57.5% (n/N = 46/80) in pts with R/R diffuse large B-cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of TAFA + LEN and rituximab for pts with R/R FL or MZL. Methods: This phase 3 double-blind, placebo-controlled, randomized study is designed to investigate whether TAFA + LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in pts with R/R FL or R/R MZL. Pts will be randomized 1:1 to receive TAFA (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) + LEN (20 mg PO QD, days 1–21/cycle for 12 cycles) and rituximab (375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or placebo (0.9% saline solution IV) + LEN and rituximab. Stratified randomization will be performed separately for pts with R/R FL and R/R MZL. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for pts with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET-CR rate (INV) at end of treatment (90 days after last treatment) and OS in pts with FL. Inclusion criteria include age ≥18 y, histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including pts with anti-CD20 refractory disease), ECOG PS ≤2, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab + LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF < 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling pts; planned enrollment is 528 pts with R/R FL and 60–90 pts with R/R MZL across North America, Europe, and Asia Pacific. Clinical trial information: NCT04680052 / EudraCT2020-004407-13.

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

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmano category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Randomized trialhigh
gptno category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Randomized trialhigh
models agreeAgreement compares identical category sets and study designs across arms.

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)0.002
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 score0.010
Threshold uncertainty score0.032

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0020.005
Insufficient payload (model declined to judge)0.0100.002

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 head0.127
GPT teacher head0.452
Teacher spread0.325 · 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

Labeled directly by 2 models reading the full record.

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".

Quick stats

Citations2
Published2022
Admission routes1
Has abstractyes

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