Anlotinib plus TQB2450 in patients with advanced refractory biliary tract cancer (BTC): An open-label, dose-escalating, and dose-expansion cohort of phase Ib trial.
Bibliographic record
Abstract
292 Background: Anti-angiogenic agents have been clinically investigated in combination with anti-PD-1/L1 mAbs due to their immuno-modulatory effects. Anlotinib (A), a potent oral multi-target tyrosine kinase inhibitor, has anti-angiogenic properties and anti-tumor efficacy with a favorable toxicity profile. The combination of A and TQB2450 (T), an anti-PD-L1 mAb, exhibited superior tumor growth suppression compared to either monotherapy in murine models. This ongoing phase 1b study cohort is aimed to assess the safety and efficacy of A+T in pts with advanced BTC. Methods: In this study cohort, patients (pts) with previously treated, advanced BTC were enrolled. A 3+3 dose escalation was used to determine the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) in a dose-escalating stage. Additional pts were enrolled in a dose-expansion stage to further establish the safety and determine the preliminary efficacy. Oral A of 10 and 12 mg was administered once daily for 14 days on / 7 days off with intravenous T of 1200 mg every 3 weeks. The primary endpoint was dose-limiting toxicity (DLT) during first cycle (first 3 weeks) to estimate the MTD, RP2D and overall response rate (ORR). Tumor response was assessed according to RECIST version 1.1 and iRECIST. The Secondary endpoints were progression-free survival (PFS), disease control rate (DCR) and safety. Results:25 pts were enrolled (8 with intrahepatic cholangiocarcinoma [IHCC]; 8 with extrahepatic cholangiocarcinoma [EHCC]; 9 with gall bladder cancer [GBC]) until August 2020. Median number of prior lines of therapy was 1 (range 1-5). During dose-escalation, no DLT was observed and 12 mg anlotinib was determined as RP2D for expansion. Among 24 evaluable pts (with at least once tumor assessment), 3 had achieved complete response (CR) and 7 had partial response (PR), which were all treated by 12 mg anlotinib plus TQB2450, 8 had stable disease (SD) and 6 had progression disease (PD). ORR was 41.67% and DCR was 75%. 10 pts were still on treatment. The median PFS was 240 days (95% CI, 83~NR).Treatment-related adverse events (TRAEs) occurred in 83.3% of pts (G3/4 in 16.7% [4/24], and leading to treatment discontinuation in 4.2% [1/24]). The most common TRAEs were hypertension (33.3%), decreased white blood cell counts (25.0%), increased TBIL (20.8%), decreased neutrophil counts (20.8%), increased DBIL (12.5%), and increased IBIL (12.5%). Conclusions: A+T had a manageable safety profile and encouraging antitumor efficacy in pts with previously treated, advanced BTC. No unexpected AEs were identified beyond the established safety profile for each agent. Clinical trial information: NCT03996408.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| 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".