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Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer.

2020· article· en· W3029117137 on OpenAlexaff
Lucy Gilbert, Ana Oaknin, Ursula A. Matulonis, Gina Mantia-Smaldone, Peter Lim, Cesar M. Castro, Diane Provencher, Sanaz Memarzadeh, Jiuzhou Wang, Brooke Esteves, Patrick A. Zweidler‐McKay, Kathleen N. Moore, David M. O’Malley

Bibliographic record

VenueJournal of Clinical Oncology · 2020
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsRoyal Victoria HospitalUniversité de MontréalMcGill University Health CentreRoyal Victoria Regional Health Centre
Fundersnot available
KeywordsMedicineBevacizumabNeutropeniaInternal medicineAdverse effectGastroenterologyOvarian cancerNauseaCancerOncologySurgeryPharmacologyChemotherapy

Abstract

fetched live from OpenAlex

6004 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥ 50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PR) (recurrence within 6 months after last platinum dose) or platinum sensitive (PS) responded to the last platinum therapy received before study entry and did not progress within 6 months) disease for whom a non-platinum based doublet would be appropriate. Methods: Pts received MIRV (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed by investigator according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 60 pts received the combination, with a median age of 60 years, and a median of 2 prior lines of systemic therapy (range 1-4). Platinum status was determined for 56 pts, with 30 (50%) considered PR and 26 (43%) considered PS; platinum status data were incomplete for 4 pts. The most common treatment related AEs (percent all grade/grade 3+) were diarrhea (65/2), blurred vision (62/3), nausea (55/0), and fatigue (55/5). The most common treatment related grade 3+ AEs were hypertension and neutropenia, (10% each); all other grade 3+ events occurred in ≤ 5% of pts. Serious AEs regardless of relationship to study drug were infrequent, with the most common events being small intestinal obstruction in 3 pts, 5% (grade 3) and pneumonitis in 3 pts, 5% (2 grade 1; 1 grade 2). Objective responses were seen in 26 pts for a confirmed overall response rate (ORR) of 43% (95% CI, 31, 57). In a subset analysis of pts with high FRα expressing tumors (n = 33), the confirmed ORR was 61% (95% CI, 42, 77), with an ORR of at least 50% in each of the PR and PS subsets. With a median follow-up of 5.5 months, the duration of response and progression free survival data are immature. Conclusions: The combination of MIRV with BEV demonstrates an encouraging ORR with a favorable tolerability profile in pts with recurrent ovarian cancer regardless of platinum sensitivity, particularly in those with tumors that express high levels of FRα. Clinical trial information: NCT02606305.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.045
GPT teacher head0.387
Teacher spread0.341 · 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 designNon-randomized 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

Citations8
Published2020
Admission routes1
Has abstractyes

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