Abstract CT216: Response to first-line (1L) pembrolizumab (pembro) + chemotherapy (chemo) in non-small cell lung cancer (NSCLC) by blood tumor mutational burden (bTMB): the phase 2 KEYNOTE-782 trial

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (8_Supplement), p.CT216-CT216
• Main Authors: Bar, Jair, Esteban, Emilio, Rodríguez-Abreu, Delvys, Aix, Santiago Ponce, Szalai, Zsuzsanna, Felip, Enriqueta, Gottfried, Maya, Pulla, Mariano Provencio, Robinson, Andrew, Fülöp, Andrea, Rao, Suman B., Camidge, D. Ross, Speranza, Giovanna, Townson, Steven M., Kobie, Julie, Ayers, Mark, Dettman, Elisha J., McDaniel, Robert, Jung, Byoungsok, Burkhardt, David, Mauntz, Ruth, Csőszi, Tibor
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-CT216

Background: 1L pembro + platinum-based chemo has shown clinical activity in metastatic NSCLC regardless of tissue tumor mutational burden (tTMB) status. bTMB assessed using circulating tumor DNA in plasma may be a surrogate for tTMB. The single-arm, phase 2 KEYNOTE-782 study (NCT03664024) evaluated the correlation of bTMB with efficacy of 1L pembro + chemo in nonsquamous NSCLC. Methods: Eligible patients (pts) had histologically or cytologically confirmed stage IV nonsquamous NSCLC with measurable disease per RECIST v1.1 and were not eligible for EGFR-, BRAF-, ROS1-, or ALK-directed therapy. Pts were not previously treated for advanced or metastatic disease, had an ECOG PS of 0 or 1, and had an evaluable biopsy sample for biomarker analysis. All pts received intravenous pembro 200 mg Q3W + platinum chemo doublet Q3W (pemetrexed 500 mg/m2 + 4 cycles of carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2). The primary objective was to evaluate the association of baseline bTMB with ORR per RECIST v1.1 by investigator assessment. Secondary objectives were to determine safety and the association of baseline bTMB with PFS per RECIST v1.1 by investigator assessment and OS. A study-specific next-generation sequencing-based assay using a 1.9 Mb/654-gene cancer panel, which includes specific lung cancer-associated gene targets, was used to measure bTMB (continuous scale) in cell-free DNA extracted from baseline plasma samples. Paired white blood cell DNA sequencing was also performed to eliminate potential clonal hematopoiesis-derived somatic mutations. Database cutoff: November 5, 2021. Results: 117 pts were enrolled; median age was 64.0 years (range, 37-85), and the majority were male (60.7%), had an ECOG PS of 1 (69.2%), and no brain metastases at baseline (92.3%). Median time from first dose to data cutoff was 19.3 months (range, 1.0-35.5). ORR was 40.2% (95% CI, 31.2-49.6; 6 CRs, 41 PRs), median PFS was 7.2 months (95% CI, 5.6-9.8), and median OS was 18.1 months (95% CI, 13.5-25.6). Treatment-related adverse events (TRAEs) occurred in 113 pts (96.6%) and grade 3-5 TRAEs occurred in 56 (47.9%). Eight pts (6.8%) died due to a TRAE (febrile neutropenia and pneumonitis [n = 2 each], and septic shock, pulmonary sepsis, general physical health deterioration, and neutropenia [n = 1 each]). bTMB data were available for 101 pts. The area under the receiver operating curve for bTMB as a continuous variable to discriminate response was 0.47 (95% CI, 0.36-0.59). The posterio