Abstract 905P
Background
MRG003 is a novel ADC composed of a humanized anti-EGFR mAb conjugated to MMAE via a vclinker. MRG003 is presently being investigated in an ongoing Ph I study.
Methods
In the Ph Ia dose escalation with 3+3 design, pts with advanced cancers received MRG003 Q3W for a maximum of 8 cycles. The starting dose of MRG003 was 0.1 mg/kg, followed by 0.3, 0.6, 1.0, 1.5, 2.0, 2.5, and 3.0 mg/kg. Ph Ib included expansion cohorts for advanced or metastatic CRC, SCCHN, and NPC who had progressed on multiple prior therapies and were treated at 2.5 mg/kg Q3W. Observations included AEs, DLT, and antitumor activity which is assessed every two cycles.
Results
A total of 22 pts were enrolled in the Ph Ia without pre-screening of EGFR positivity; and a total of 39 pts with CRC (12), SCCHN (13), and NPC (14) were enrolled in Ph Ib with pre-screening of EGFR by IHC. The median age of pts was 56.5 and 52 years in Ia and Ib, respectively. The median number of prior therapies was 3 (1, 6). The RP2D identified was 2.5 mg/kg for Ph Ib. In Ph I, commonly observed TRAEs that occurred in ≥20% of pts were rash (39%); AST increase (38%); alopecia (33%); appetite decrease (31%); ALT increase (30%); pruritus (26%); myalgia (21%); asthenia, pyrexia, and WBC count decrease (20%). The most common TRAEs ≥ Grade 3 were reported in 14 pts (23%). All ≥ Grade 3 AEs occurred in the 2.5 mg/kg cohort. Among 18 of 22 pts who had tumor evaluation in Ph Ia, the ORR was 6% and DCR was 33%; Among 27 of 39 pts evaluable for efficacy in Ph Ib, the BOR was 11 PR (8 confirmed) and 9 SD, the ORR was 30% and DCR was 63%. The ORR was 40% and DCR was 80% for SCCHN, and the ORR was 44% and DCR was 78% for NPC. The enrollment of Ph Ib dose expansion has completed and the pts are being followed up.
Conclusions
The Ph I study of MRG003 showed manageable safety profile and encouraging antitumor activity in pts with advanced heavily pretreated solid tumors including NPC and SCCHN, which will be further investigated in Ph II studies. After comprehensive evaluation of the safety data from all pts enrolled in the Ph Ib, MRG003 is expected to have improved safety and tolerability at 2.0 mg/kg compared to 2.5 mg/kg. The sponsor will further explore 2.0 mg/kg as the possible RP2D in future Ph II studies.
Clinical trial identification
CTR20180310.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Miracogen Inc.
Funding
Shanghai Miracogen Inc.
Disclosure
Y. Wang: Financial Interests, Personal, Full or part-time Employment: Shanghai Miracogen Inc. M. Li: Financial Interests, Personal, Full or part-time Employment: Shanghai Miracogen Inc. F. Hausheer: Financial Interests, Personal, Full or part-time Employment: Lepu Biopharma Co., Ltd. C. Hu: Financial Interests, Personal, Full or part-time Employment: Shanghai Miracogen Inc. All other authors have declared no conflicts of interest.