Abstract 5782: Effect of tremelimumab in combination with durvalumab and chemotherapy in heterogeneous metastatic lesions: A volumetric analysis

Abstract Background: Patients with metastatic non-small cell lung cancer (mNSCLC) in 1L therapy treated with a limited course of five cycles of the anti-CTLA-4 antibody tremelimumab (T) added to durvalumab (D) plus four cycles of platinum-based chemotherapy (CTx) experienced a reduction in the risk of death versus CTx alone, especially in non-squamous (NSq) patients. One potential mechanism of anti-CTLA-4 is the diversification of the T-cell response, which may help address tumor heterogeneity more effectively. RECIST based measurements may fail to capture this impact by mainly quantifying target lesions in 2D. Here we assess the ability of volumetric radiographic data to more comprehensively assess the impact of anti-CTLA-4 treatment on tumor growth. Methods: We analyzed the Computed Tomography (CT) images from 369 NSq patients in the T+D+CTx and D+CTx arms of the Poseidon Phase III trial. Five experienced radiologists annotated and segmented up to 10 lesions in the baseline scans (start of the induction phase), including the RECIST-based target lesions as well as additional measurable non-target lesions (a maximum of 4 lesions per organ). These segmented lesions were tracked, and new lesions were annotated in the follow-up scans of 316 patients at week 12 (end of induction phase) and 276 patients at week 20 (maintenance phase). 3D volume of lesions as well as the RECIST 1.1 lesion diameters were noted and the percentage change in these metrics were observed and compared across the selected trial arms. Results In comparing the T+D+CTx arm to the D+CTx arm, we observed a significantly larger median volumetric reduction at the end of the induction phase, at both lesion level (69.5% vs 53.4%, p<0.001) as well as patient level (65.0% vs 52.3%, p < 0.001). Analysis of the volumetric change in metastatic lesions in the liver and adrenal glands showed a similar trend of deeper response in patients given T+D+CTx as compared to D+CTx which was not observed with the 2D diametric change. This deeper response was noted in both the Programmed death-ligand1 (PD-L1, used as a randomization covariate) < 1% and >/=1-49% groups comparing T+D+CTx to D+CTx cohort. Analysis of change in tumor burden from week-12 to week-20 (after the end of CTx) showed that a larger proportion of T+D+CTx treated patients (60.7%) continued with tumor volumetric reduction compared to patients in D+CTx arm (44.6%). Conclusions This volumetric analysis offers more accurate quantification of tumor size change than the 2D diametric approach. This analysis of the NSq patients suggests that tremelimumab in combination with durvalumab may result in a deeper and longer response in adult patients with Stage IV (metastatic) NSCLC compared to durvalumab-only. Citation Format: Qin Li, Harish RaviPrakash, Kedar Patwardhan, Jamie MacKay, Amreen Shakur, Zhiyang Wei, James Parkin, Michael Parker, Shaneil V. Patel, Ross Stewart. Effect of tremelimumab in combination with durvalumab and chemotherapy in heterogeneous metastatic lesions: A volumetric analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5782.