Discussion
NSCLC, asthenia, nausea, gastroesophageal junction adenocarcinoma, abdominal pain, pancreatic cancer
MULTIPLE MYELOMA, BAND KERATOPATHY, DISEASE, SOLID TUMORS, PANCREATIC CANCER, GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA, NSCLC, PERIPHERAL NEUROPATHY, GASTRIC CANCER
The results from cohorts Q2W-LD and Q3W of this phase I dose-escalation trial in patients with advanced solid tumors confirm and extend the understanding of the DLTs, safety, and pharmacokinetics of tusamitamab ravtansine established in the earlier first-in-human main dose-escalation study results (The most common TEAEs were asthenia, nausea, abdominal pain, and keratopathy in both cohorts. Grade 1 peripheral neuropathy was also observed in both cohorts [incidence 21.4% in the Q2W-LD cohort (Prophylactic measures were used during the main Q2W (A variety of ocular AEs have been reported with a range of ADCs that have diverse biological targets and cytotoxic payloads (In a phase II trial in patients with multiple myeloma, severe (grade 3/4) corneal AEs were reported in 46% of patients treated with an ADC (belantamab mafodotin) that targets B-cell maturation antigen, a marker that is expressed exclusively on malignant plasma cells (No patients in either cohort had objective responses, although stable disease was observed in 10 of 25 (40.0%) evaluable patients in cohort Q2W-LD and 6 of 13 (46.2%) evaluable patients in cohort Q3W. It is unclear why objective responses were not observed with the dosing schedules in the current study, although the heavily pretreated, and potentially refractory, patient population in this study may have been a contributing factor. Ongoing clinical trials are evaluating responses to tusamitamab ravtansine treatment in patients with NSCLC, gastric cancer, or pancreatic cancer and may provide additional insight. Partial responses were observed in 3 patients enrolled in the main dose-escalation cohort who were treated with 100 or 120 mg/mConsistent with observations in the main Q2W dose-escalation cohort, exposure (CThe collective results of the dose-escalation cohorts presented in the present and previous analyses have practical implications for the clinical development of tusamitamab ravtansine. The drug exposure profile and MTD have now been determined for three different regimens, and the DLT of tusamitamab ravtansine was consistent in each cohort. This provides flexibility when designing dosing schedules for use in future trials and in combination with other agents. To this end, the results of this study have informed the design of further studies of tusamitamab ravtansine in patients with solid tumors. Ongoing trials are investigating the safety and efficacy of tusamitamab ravtansine Q2W as monotherapy (CARMEN-LC03; NCT04154956), Q2W in combination with ramucirumab (CARMEN-LC04; NCT04394624), and Q3W in combination with pembrolizumab (CARMEN-LC05; NCT04524689) in patients with NSCLC; and Q2W-LD in patients with advanced gastric or gastroesophageal junction adenocarcinoma (CARMEN-GC01; NCT05071053; refs. In conclusion, the MTD of tusamitamab ravtansine was 170 mg/m