Risk factors for venous thromboembolism (VTE) among patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) receiving amivantamab plus lazertinib versus either agent alone.

person Nicolas Girard Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France info_outline Nicolas Girard, Byoung Chul Cho, Alexander I. Spira, Catherine A. Shu, Rachel E. Sanborn, Joel W. Neal, Melina Elpi Marmarelis, Joshua K. Sabari, Saiama Naheed Waqar, Misako Nagasaka, James Chih-Hsin Yang, Shun Lu, Pritam Kambuj, Jeffrey Sanchez, Lahila-Carina Ojeda, John Xie, Parthiv Mahadevia, Joshua Michael Bauml, Roland E. Knoblauch, Hidetoshi Hayashi

Authors person Nicolas Girard Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France info_outline Nicolas Girard, Byoung Chul Cho, Alexander I. Spira, Catherine A. Shu, Rachel E. Sanborn, Joel W. Neal, Melina Elpi Marmarelis, Joshua K. Sabari, Saiama Naheed Waqar, Misako Nagasaka, James Chih-Hsin Yang, Shun Lu, Pritam Kambuj, Jeffrey Sanchez, Lahila-Carina Ojeda, John Xie, Parthiv Mahadevia, Joshua Michael Bauml, Roland E. Knoblauch, Hidetoshi Hayashi Organizations Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), Virginia Cancer Specialists, Fairfax, VA, Columbia University Medical Center, New York, NY, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, Stanford University Medical Center, Stanford, CA, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, NYU Langone Health, New York, NY, Division of Oncology, Washington University School of Medicine, St. Louis, MO, University of California Irvine School of Medicine, Orange, CA, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China, Janssen R&D, Raritan, NJ, Janssen R&D, Spring House, PA, Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Janssen R&D, LLC Background: Amivantamab (ami), an EGFR and cMET bispecific antibody with immune cell-directing activity, and lazertinib (laz), a CNS-penetrant 3 rd -generation EGFR tyrosine kinase inhibitor have shown clinical activity in biomarker-selected patients (pts) with advanced NSCLC. Antitumor activity has been suggested to be improved when the agents are given in combination (Leighl Ann Oncol 2021;32:suppl_5, 1192MO). We examined the incidence of VTE, a common adverse event (AE) among pts with lung cancer, for those receiving ami monotherapy, laz monotherapy, and ami+laz to investigate if there is elevated risk and understand potential predisposing risk factors. Methods: CHRYSALIS (NCT02609776; ami monotherapy and ami+laz), CHRYSALIS-2 (NCT04077463; ami+laz), and LASER201 (NCT04075396; laz monotherapy) are ongoing open-label studies of locally advanced/metastatic NSCLC. Two descriptive, univariate risk analyses were performed, with the primary analysis including all treatment-emergent VTE events (grouped term) and a secondary analysis that excluded VTE events occurring after progression of disease (PD) or within 30 days prior to PD. Results: This analysis included 560 pts who received ami monotherapy, 536 ami+laz, and 252 laz monotherapy, predominantly in the TKI-relapsed setting. The incidence of VTE events of any grade was numerically higher in pts who received ami+laz (21%) than those who received ami (11%) or laz (11%) monotherapy. The median time to onset of the first VTE event was 84.5 days for ami, 79 days for ami+laz, and 170 days for laz. The majority (64%) of ami+laz pts had VTE events in the first 4 months. The most common VTE events by preferred term were pulmonary embolism and deep vein thrombosis. The incidence of grade ≥3 VTE events was comparable among pts receiving ami (5%), ami+laz (6%), and laz (6%), and there were no grade 5 VTE events for ami+laz. The overall incidence of serious VTE AEs was low (ami, 3%; ami+laz, 5%; laz, 4%). There were 6 discontinuations due to VTE, 1 (0.2%) ami, 2 (0.4%) for ami+laz, and 3 (1.2%) laz. In the primary analysis, age ≥60 years was a significant risk factor ( P < 0.05). In the secondary analysis, age ≥60 years, ECOG performance status of 1 (vs 0), and response to therapy (partial response or better) were significant risk factors ( P < 0.05). Conclusions: Lung cancer diagnosis is a known risk factor for VTE. In a review across clinical trials, single-arm cohort data suggest there is a numerically higher incidence of VTE for ami+laz compared with each monotherapy. Age ≥60 years, ECOG performance status, and response to treatment are potential risk factors. The relationship between response and VTE is emerging and may reflect possible immune or inflammatory-mediated mechanisms. Further efforts to understand VTE-associated risk factors in randomized clinical trials are ongoing. Clinical trial information: NCT02609776, NCT04077463 , NCT04075396 .