A multicenter, open-label, phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of JMT-101 in patients (pts) with advanced colorectal cancer (ACC).

e16025 Background: JMT101 is a fully human monoclonal IgG1 antibody targeting epidermal growth factor receptor (EGFR). This study aimed to evaluate the safety and tolerability of JMT101 alone or in combination with chemotherapy in ACC. Methods: This is an open label, dose-escalating, phase I clinical trial. The pts with ACC and naïve to systemic EGFR-targeted therapy were assigned to receive JMT101 monotherapy (JMT101 group, pts with wild-type RAS ACC and had experienced failure of at least one standard regimen) or JMT101 in combination with mFOLFOX6/FOLFIRI (combination group, pts with wild-type RAS/non-BRAF V600E mutant ACC). JMT101 was infused intravenously by accelerated titration and traditional "3+3" dose-escalation scheme. The initial dose of JMT101 monotherapy was 0.5 mg/kg (q1w), and sequentially escalated to 2.0, 4.0, 6.0, 8.0, and 10.0 mg/kg (q2w). Until the dose of JMT101 group was escalated to the higher dose and sufficient safety data were obtained, the dose of the combination group would be escalated sequentially from 6.0, 8.0, to 10.0 mg/kg (q2w). The primary endpoints were safety and tolerability. The secondary endpoints were clinical efficacy and pharmacokinetic parameters. Results: From April 2017 to December 2019, 16 enrolled pts in JMT101 group (13 males, 3 females, median age 59.5 [27-64] years) and 7 in combination group (4 males, 3 females, median age 49 [39-68] years) were evaluable. The dose of JMT101 was escalated to 10.0, 8.0, 6.0 mg/kg in JMT101 group, mFOLFOX6 group and FOLFIRI group, respectively. Dose-limiting toxicity was not observed, maximum tolerated dose was not reached, and treatment-related SAE was not reported so far. JMT101 monotherapy and combination therapy were associated with grade 1 (15 and 7 cases), grade 2 (10 and 7 cases), and grade 3 (5 and 5 cases) AEs. In all groups, the most common AEs were skin rash (81.3% [13/16] in JMT101 group, 100% [7/7] in combination group), proteinuria (62.5% [10/16] in JMT101 group, 28.6% [2/7] in combination group) and oral mucositis (86.0% [6/7] in combination group). JMT101 monotherapy and combination therapy resulted in partial response (2 and 4 pts), objective response rate (12.5% and 57.1%), disease control rate (56.2% and 100%), and disease control > 24 weeks (4 and 3 pts). Conclusions: JMT101 shows good safety, tolerability, and antitumor activity in pts with ACC. Clinical trial information: 20160904 .