Abstract 271P
Background
MRG002 is an ADC composed of a humanized anti-HER2 mAb conjugated to MMAE via a vclinker. MRG002 is presently being investigated as monotherapy in an ongoing phase I study for safety, tolerability, PK, and preliminary antitumor activity in patients (pts) with HER2+ advanced or metastatic solid tumors.
Methods
In phase Ia dose escalation utilizing a “3+3” design, a total of 25 pts with BC (19), SGC (3), GC (2), and CRC (1) were enrolled to identify MTD/RP2D. The median age was 53 (30, 66) years. The median number of prior therapies was 5 (1, 11). The starting dose of MRG002 was 0.3 mg/kg, followed by 0.6, 1.2, 1.8, 2.2, 2.6, and 3.0 mg/kg, all pts with BC and GC had HER2+ per CAP guidelines. For the other cancers, pts had an IHC status of 2+ or 3+, regardless of HER2 FISH results. Each pt received MRG002 Q3W for a maximum of 8 cycles.
Results
Commonly observed TRAEs were neutrophil count decrease (56%), AST increase (56%), WBC decrease (56%), lactate dehydrogenase increase (44%), alopecia (44%), CPK increase (40%), ALT increase (36%), triglyceride increase (32%), cholesterol increase (32%), GGT increase (32%), appetite decrease (32%), and hypoaesthesia (32%). Majority of AEs were mild to moderate in severity. The most commonly reported TRAEs ≥ Grade 3 were neutrophil count decrease and triglycerides increase in 3 pts (12%), respectively. The treatment-related SAEs were reported in 6 pts (24%) including GGT increase, AST/ALT increase, neutrophil count decrease, LEVF decrease, fatigue, peripheral neuropathy. There was no death due to AEs. Among 21 pts who had at least one tumor assessment, 9 PR (43%), 8 SD (38%), and 4 PD (19%). The investigator assessed ORR was 43% and the DCR was 81%. Of these 21 pts, 16 pts were HER2+ breast cancer, 8 PR, 5 SD, and ORR was 50% (8/16), DCR was 81%(13/16). There were two DLTs at 3.0 mg/kg including LVEF decrease and CPK elevation. Accordingly, the RP2D determined at 2.6 mg/kg which is currently being evaluated in the phase Ib dose expansion.
Conclusions
The dose escalation of MRG002 showed manageable safety profile and encouraging antitumor activity in pts with HER2+ solid tumors including BC, GC and other cancer types, which will be further investigated in phase II studies.
Clinical trial identification
CTR20181778.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Miracogen Inc.
Funding
Shanghai Miracogen Inc.
Disclosure
S. Zhang, J. Sun, M. Li, C. Hu: 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. All other authors have declared no conflicts of interest.