A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors.
Bibliographic record
Abstract
101 Background: OX40 is a co-stimulatory receptor that is transiently expressed by T cells upon antigen recognition. In murine models, OX40 engagement by an agonist anti-OX40 antibody can promote durable tumor regression associated with co-stimulation of effector T cells and reduction of regulatory T cells. This dual mechanism of action is predicted to complement the activity of PD-L1 blockade. MOXR0916 is a humanized effector-competent agonist IgG1 monoclonal antibody (mAb) that targets OX40 and atezolizumab is an engineered humanized IgG1 mAb that targets PD-L1. Methods: A Phase I, open-label, multicenter study was conducted to evaluate the safety and pharmacokinetics (PK) of MOXR0916 and atezolizumab in patients (pts) with locally advanced or metastatic solid tumors. A 3+3 dose-escalation was conducted with a 21-day window to evaluate dose-limiting toxicity (DLT). Escalating doses of MOXR0916 in combination with a fixed 1200 mg dose of atezolizumab were administered every 3 weeks (q3w). An expansion cohort to enable immune profiling of serial tumor biopsies was also enrolled. Prior immunotherapy with adequate washout was allowed if there was no history of Grade (G) ≥ 3 immune-mediated adverse events (AEs). Results: As of 7 Jan 2016, 25 pts were treated in 7 dose escalation cohorts (dose levels 0.8 to 600 mg) and 19 additional pts were treated in a serial biopsy cohort. The median number of prior therapies for metastatic disease was 2 (range 0-7), and 5 pts had received prior PD-1/PD-L1 antibodies. No DLTs, G4/5 AEs attributed to study treatment, or related AEs leading to treatment discontinuation were reported. The majority of treatment-related AEs were G1 in severity; 1 related G3 event (pneumonitis responsive to corticosteroids) was reported. The PK of each mAb was consistent with its established single agent profile. Objective responses were observed; clinical and biomarker data will be updated. The regimen selected for dose expansion is MOXR0916 300 mg + atezolizumab 1200 mg q3w. Conclusions: The combination of MOXR0916 and atezolizumab was well-tolerated. An expansion phase, with each agent administered at its recommended monotherapy dose, is ongoing in selected tumor types. Clinical trial information: NCT02410512.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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".