PI-041 - BENEFIT-RISK OF FLAT-DOSING OF NIVOLUMAB IN COMBINATION WITH IPILIMUMAB IN THORACIC CANCER IMMUNOTHERAPY (1L METASTATIC NON-SMALL-CELL LUNG CANCER AND 1L UNRESECTABLE MALIGNANT PLEURAL MESOTHELIOMA).

A. Tendolkar¹, J. Shi¹, M. Osawa¹, Y. Zhao¹, P. Vuppala², Y. Feng³, A. Roy¹, J. Sheng¹; ¹Bristol Myers Squibb, Lawrenceville, NJ, USA, ²Daiichi Sankyo, Basking Ridge, NJ, USA, ³GenMab, Princeton, NJ, USA.

Background: Nivolumab (Nivo), a human IgG4 monoclonal antibody that blocks PD 1, has been shown to be safe and efficacious in various tumor types. This study is to support the benefit-risk assessment of flat-dose regimen of Nivo 360 mg every 3 weeks (Q3W), relative to the body weight-based dosing regimen of 3 mg/kg Q2W, when dosed with ipilimumab (Ipi) 1 mg/kg Q6W in patients with first-line (1L) metastatic non-small-cell lung cancer (mNSCLC) or 1L unresectable malignant pleural mesothelioma (uMPM).

Methods: An updated Nivo population PK (PPK) model was used to predict and compare Nivo exposures following flat-dosing versus body weight-based dosing regimen. The impact of differences in Nivo exposures on efficacy and safety was further assessed by Cox proportional-hazards model-based exposure-response (E-R) analyses. In addition, subgroup analyses by body weight categories and exposure quartiles were conducted to assess the efficacy and safety of Nivo + Ipi in patients with 1L mNSCLC and 1L uMPM.

Results: The Nivo exposures (Cmax1), if dosed with 360 mg Q3W, were predicted to be ~66% and ~67% higher than those following 3 mg/kg Q2W, in 1L mNSCLC and 1L uMPM, respectively. E-R analyses demonstrated comparable efficacy and safety profiles between Nivo 360mg Q3W vs 3mg/kg Q2W, in the presence of Ipi 1mg/kg Q6W, in both 1L mNSCLC and 1L uMPM. Further, the subgroup analysis showed efficacy and safety were not associated with body weight categories, and safety was not associated with exposure quartiles.

Conclusion: Pharmacometric analyses and subgroup analyses demonstrated comparable efficacy and safety between the two dosing regimens. The Nivo 360 mg Q3W flat-dosing regimen provides an alternative to the clinically tested weight-based dosing regimens for patients with 1L mNSCLC and 1L uMPM.