A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors.

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.