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KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) plus olaparib vs pembro plus chemotherapy after induction with first-line pembro plus chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC).

2020· article· en· W3032723625 on OpenAlexaff
Hope S. Rugo, Antonio Llombart‐Cussac, Fabrice André, Mark E. Robson, Shigehira Saji, Nadia Harbeck, Peter Schmid, David W. Cescon, Jin Seok Ahn, Rita Nanda, Aditya Bardia, Fan Li, Jaime Mejia, Vassiliki Karantza

Bibliographic record

VenueJournal of Clinical Oncology · 2020
Typearticle
Languageen
FieldMedicine
TopicPARP inhibition in cancer therapy
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsMedicineGemcitabineOncologyChemotherapyInternal medicineCarboplatinPembrolizumabOlaparibInduction chemotherapyImmunotherapyCancerCisplatin

Abstract

fetched live from OpenAlex

TPS596 Background: Combination therapy with immunotherapy + chemotherapy is a promising approach for first-line (1L) treatment of locally recurrent, inoperable TNBC or metastatic TNBC (mTNBC). However, an unmet need exists for effective and tolerable maintenance regimens in mTNBC to sustain clinical benefit after induction therapy and avoid potential toxicity or resistance in response to prolonged chemotherapy. The PARP inhibitor olaparib has demonstrated efficacy in the maintenance setting for multiple platinum-sensitive tumors, and the prevalence of BRCA mutations in TNBC may make these tumors particularly sensitive to DNA-damaging agents. Moreover, previous data suggest that combination therapy with olaparib and the PD-1 inhibitor pembro may have clinical benefits. KEYLYNK-009 (NCT04191135) is a phase II/III, open-label, randomized study of pembro + olaparib or pembro + chemotherapy after induction with 1L pembro + chemotherapy in patients with locally recurrent, inoperable TNBC or mTNBC. Methods: This 2-in-1 study design will enroll ~317 patients in phase II; if a planned efficacy boundary is met, ~615 additional patients will be enrolled in phase III. Patients eligible for induction therapy must have measurable, locally recurrent, inoperable TNBC that cannot be treated with curative intent or mTNBC previously untreated with chemotherapy in the metastatic setting. All patients will receive up to 6 cycles of induction therapy with pembro 200 mg every 3 wk (Q3W) + chemotherapy (carboplatin AUC 2 + gemcitabine 1000 mg/m2). Patients eligible for postinduction treatment must achieve complete or partial response or maintain stable disease during induction after 4-6 treatment cycles, with ECOG PS 0/1 and no grade >1 toxicities related to induction therapy (excluding alopecia, Hb ≥9.0 g/dL, grade 2 hyper-/hypothyroidism, or grade 2 hyperglycemia). These patients will be randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or continue pembro + chemotherapy (same as induction regimen). Olaparib and chemotherapy may continue until progression or unacceptable toxicity; pembro may continue for ≤35 cycles (including induction), unacceptable toxicity, or progression. Phase III dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints include OS and PFS in patients with BRCAm, health-related quality of life, and safety. Enrollment is ongoing. Clinical trial information: NCT04191135 .

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)0.002
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 score0.012
Threshold uncertainty score0.041

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0020.001
Research integrity0.0020.005
Insufficient payload (model declined to judge)0.0120.002

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 head0.112
GPT teacher head0.447
Teacher spread0.335 · 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".

Quick stats

Citations19
Published2020
Admission routes1
Has abstractyes

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