Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase II LEAP-005 study.
Bibliographic record
Abstract
321 Background: Second-line treatment options for patients with biliary tract cancers (BTC) are limited. Lenvatinib, an anti-angiogenic multikinase inhibitor, in combination with the programmed death-1 immune checkpoint inhibitor pembrolizumab, has demonstrated promising antitumor activity with a manageable safety profile in patients with select advanced solid tumors. LEAP-005 (NCT03797326) is evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors; here we present results from the BTC cohort of LEAP-005. Methods: In this nonrandomized, open-label, phase II study, eligible patients were aged ≥18 years with histologically or cytologically documented advanced (metastatic and/or unresectable) BTC with disease progression after 1 prior line of therapy, measurable disease per RECIST v1.1, ECOG PS of 0‒1, and tissue sample evaluable for PD-L1 expression. Patients received lenvatinib 20 mg once daily plus pembrolizumab 200 mg Q3W for up to 35 cycles (approximately 2 years) or until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. Treatment with lenvatinib could continue beyond 2 years in patients experiencing clinical benefit. Primary endpoints were ORR (per RECIST v1.1 by blinded independent central review) and safety. Secondary endpoints were the disease control rate (DCR; comprising CR, PR, and SD), duration of response (DOR), PFS, and OS. Tumor imaging was performed Q9W from treatment initiation for 54 weeks, then Q12W to week 102, and Q24W thereafter. Results: 31 patients were enrolled in the BTC cohort (ECOG PS 1, 55%; 84% ex-US). As of April 10, 2020, median time from first dose to data cutoff (DCO) was 9.5 months (range, 3.1‒11.9), with 16 patients on treatment at DCO. There were 3 (10%) PRs and 18 (58%) SDs. ORR was 10% (95% CI, 2‒26), and DCR was 68% (95% CI, 49‒83). Median DOR was 5.3 months (range, 2.1+ to 6.2). Median PFS was 6.1 months (95% CI, 2.1‒6.4). Median OS was 8.6 months (95% CI, 5.6 to NR). Treatment-related AEs occurred in 30 patients (97%), including 15 (48%) who had grade 3‒4 AEs; there were no treatment-related deaths. 2 (6%) discontinued treatment due to treatment-related AEs (myocarditis, pyrexia; n = 1 each). The most frequent treatment-related AEs were hypertension (42%), dysphonia (39%), diarrhea (32%), fatigue (32%), and nausea (32%). 14 patients (45%) had immune-mediated AEs and 1 patient (3%) had an infusion-related reaction. Conclusions: Lenvatinib plus pembrolizumab demonstrated encouraging efficacy and manageable toxicity in patients with advanced BTC who had received 1 line of prior therapy. Based on these data, enrollment in the BTC cohort has been expanded to 100 patients. Clinical trial information: NCT03797326.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
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 source (direct Gemma or distilled Codex), 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".