KEYNOTE-B49: A phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy in patients with HR+/HER2- locally recurrent inoperable or metastatic breast cancer.
Bibliographic record
Abstract
TPS1118 Background: HR+/HER2− advanced breast cancer that progresses on endocrine therapy is treated with chemotherapy (chemo). The phase 1b KEYNOTE-028 trial showed durable activity with pembrolizumab (pembro) monotherapy in previously treated HR+/HER2−, PD-L1–positive (combined positive score [CPS] ≥1) advanced breast cancer. KEYNOTE-B49 (NCT04895358) is a phase 3, randomized, double-blind study of pembro + chemo vs placebo (pbo) + chemo in centrally assessed PD-L1–positive, HR+/HER2− locally recurrent inoperable or metastatic breast cancer (mBC) after progression on prior endocrine therapy. Methods: ∼800 patients (pts) with HR+/HER2− locally recurrent inoperable or mBC who are candidates for chemo (no prior chemo for metastatic disease) with PD-L1 CPS ≥1 and documented progression on prior endocrine therapy will be enrolled. Prior endocrine therapy comprises ≥2 lines (≥1 in combination with a CDK4/6 inhibitor) in the metastatic setting or 1 line with CDK4/6 inhibitor treatment for mBC in pts who had a relapse within 24 mo of primary surgery. Pts without prior CDK4/6 inhibitor treatment may enroll if they had progressed within 6 mo of starting endocrine therapy for metastatic disease and had previously relapsed within 24 mo of primary tumor surgery while on adjuvant endocrine therapy. Pts are randomized 1:1 to receive pembro 200 mg IV or pbo Q3W, each in combination with investigator’s choice of chemo: paclitaxel 90 mg/m 2 IV on days 1, 8, and 15 Q4W; nab-paclitaxel 100 mg/m 2 IV on days 1, 8, and 15 Q4W; liposomal doxorubicin 50 mg/m 2 IV on day 1 Q4W; or capecitabine 1000 mg/m 2 PO BID on days 1–14 Q3W. Randomization is stratified by tumor PD-L1 (CPS 1–9 vs ≥10), presence of visceral metastases (yes vs no), and chemo on-study (taxanes vs liposomal doxorubicin vs capecitabine). Treatment is continued until disease progression, unacceptable toxicity, withdrawal, or, for pembro/pbo, completion of 35 cycles (̃2 years); chemo can be continued per investigator discretion. Tumor PD-L1 status is determined centrally using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies; Carpinteria, CA, USA). Radiologic assessments are performed Q9W for 54 wk and then Q12W thereafter. AEs occurring from randomization until 30 d after treatment discontinuation (90 d for serious AEs) are graded per NCI-CTCAE v 5.0. Primary endpoints are PFS per RECIST v1.1 by BICR and OS in pts with PD-L1 CPS ≥10 and ≥1 tumors, separately. Enrollment is ongoing at 204 international sites. Clinical trial information: NCT04895358.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".