30P OSE279, a PD-1-blocking monoclonal antibody, as future backbone of a bifunctional checkpoint inhibitor platform: Preliminary results of a first-in-human (FIH) study in subjects with advanced malignancies
Bibliographic record
Abstract
Anti-PD-1 antibodies have shown significant clinical efficacy with manageable safety. OSE279 is a humanized S228P- IgG4 monoclonal bivalent antibody against PD-1 which will be further used as the anti-PD-1 backbone component of a bifunctional checkpoint inhibitor BiCKI ® platform. A FIH study investigating OSE279 is ongoing, evaluating 2 Dose Levels (DLs) of 100 and 300 mg given q3w and 1 DL of 600 mg q6w, according to BOIN design, in subjects with advanced malignancies who progressed on standard treatments, and for which anti-PD1/PDL1 have shown efficacy but are not locally available. Primary objective is to determine the MTD and/or Recommended Phase 2 Doses (RP2Ds). Secondary objectives are efficacy, safety, PK and PD profiles. Dose-Limiting Toxicity (DLT) period is 21 days. 300 mg was declared RP2D for a q3w regimen, with a DLT of gr3 hepatitis in 1/7 patients, as previously reported. We now report the selection of a second RP2D of 600 mg q6w with an update on safety and preliminary efficacy. In this FIH study as of November 2023, 19 subjects were treated, with 12 tumor types, the most frequent being Soft Tissue Sarcoma (n=4) and anal Squamous Cell Carcinoma (SCC n=3). Median age was 61y (range 34-77), 10/19 patients (52.6%) were female, median number of prior metastatic lines was 2 (range 1-6). At 600 mg q6w no DLTs were reported in 10 patients. Treatment-Related Adverse Events (TRAEs) occurred in 14/19 patients (73.7%). Serious TRAEs of pneumonitis gr2 and hepatitis gr3 (both at 300mg q3w), and creatinine increased gr2 (at 600 mg/q6w) occurred in 3/19 patients (15.8%). 3 confirmed PR were observed in patients with HCC (300mg/q3w), Undifferentiated Pleomorphic Sarcoma and anal SCC (both 600 mg/q6w). SD was reported in 8 patients. Treatment is ongoing in 9 patients. PK showed dose-proportionality and favorable exposure; sustained RO was observed. In this FIH study, OSE279 showed a favorable safety profile with signs of efficacy in the first 19 patients treated. 600 mg q6w has been selected as second RP2D. PK and PD profiles were according to modelling. New cohorts testing combinations, including with cancer vaccine, are planned.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".