Pharmacokinetics and biomarker analysis from a phase 1/2 open-label study of the anti-GPC3 T-cell engager SAR444200, in patients with advanced solid tumors.
Bibliographic record
Abstract
2579 Background: SAR444200 is a novel NANOBODY T cell engager that simultaneously binds TCRαβ and glypican-3 (GPC3) to co-engage T cells with GPC3-expressing tumor cells, resulting in T cell-dependent cellular cytotoxicity. Here we present updated safety, pharmacokinetics (PK) and biomarker data from 6 and 5 dose levels (DL), respectively in patients with advanced solid tumors in the dose escalation cohort (Part 1A) from the first-in-human Phase 1/2 trial (NCT05450562). Methods: This ongoing Phase 1/2 trial evaluated open label, intravenously administered SAR444200 (every week with lead-in doses) at DL1 (3 mg), DL1A (1 mg), DL2A (2.5 mg), DL3A (4.5 mg), DL4A (18 mg), and DL5A (36 mg) in adult patients with GPC3+ solid tumors. On study imaging was performed every 9 weeks after the date of first infusion of SAR444200. Whole blood samples were collected to assess the plasma concentrations of SAR444200 and for biomarker analysis. PK analysis was performed with electrochemiluminescence-based total PK assay using Meso Scale Discovery platform. Anti-drug antibody (ADA) monitoring was performed using a PandA assay. Results: As of 19 January 2024, a total of 24 patients with GPC3+ solid tumors received SAR444200, 4 patients per DL (DL1, DL1A, DL2A, DL3A, DL4A, DL5A). Most of the patients (17 patients, 71%) had hepatocellular carcinoma. No dose-limiting toxicities were observed. Twenty-two patients (92%) reported treatment-related adverse events (TRAEs) of any grade, including three patients with a serious TRAE (2 events with hospitalization prolongation for a Grade 1 and 2 cytokine release syndrome [CRS] that recovered completely without and with Tocilizumab, respectively, 1 event with pneumonitis Grade 3). All CRS (19 patients, 79%) and infusion-related reaction (7 patients, 29%) were Grade 1 or 2. Cmax was observed at the end or shortly after completion of infusion. The maximum ADA titer, though high, stabilized despite the target dose increased from Cycle 2. Biomarker analysis showed an increase of interleukin-6 and interferon gamma during lead-in doses, supporting CRS. Cytokines declined after Cycle 1. Among 14 HCC patients with baseline alpha-fatal protein (AFP) higher than 20 ng/ml, 4 (29%) had at least a 20% AFP decrease on treatment. Two patients (both with HCC) have been on study drug for more than 6 months. Conclusions: These results suggest that SAR444200 is tolerable at the tested dose levels in patients with GPC3+ advanced solid tumors. Dose escalation continues at this time. Clinical trial information: NCT05450562 .
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".