Safety and efficacy of TQB2102, a novel bispecific anti-HER2 antibody–drug conjugate, in patients with advanced solid tumors: Preliminary data from the first-in-human phase 1 trial.

3003 Background: TQB2102 is an antibody-drug conjugate (ADC) comprised of a recombinant, humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody conjugated to a topoisomerase I inhibitor via an enzyme-cleavable linker. The bispecific antibody component can target both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2. We conducted a multicenter, dose escalation and expansion first-in human (FIH) phase 1 study of TQB2102 in advanced solid tumors. Methods: In the dose escalation phase, eligible patients (pts) with advanced solid tumors whose disease had progressed after standard systemic treatments, were enrolled in a 3+3 dose escalation study of TQB2102(1.5, 3, 4.5, 6, 7.5 or 9 mg/kg) IV, every 3wks (Q3W). In the dose expansion phase, pts with HER2 positive cancers and HER2 low (HER2 1+ or HER2 2+ and FISH negative) metastatic breast cancer (MBC) received the selected recommended phase 2 dose (RP2D). The primary objectives were to evaluate the safety and tolerability, dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of TQB2102. Results: As of October 1, 2024, 181pts (41 pts in dose escalation phase and 140 pts in dose expansion phase) were enrolled from 12 centers. Most common tumor types included MBC (N = 80), Colorectal cancer (N = 37) and Gastric cancer (N = 23).Twenty-five (31%) MBC received prior anti-HER2 ADCs, including 21 pts received T-DM1, 8 pts received DS-8201.The median duration of follow-up was 8.15 months. TQB2102 was well-tolerated with no DLTs occurred and MTD was not reached. The most common (occurring in ≥5%) grade ≥3 AEs were neutrophil count decrease (21.7%), WBC count decreased (10.6%), anemia (8.9%), platelet count decreased (6.1%), diarrhea (5.0%). Only one patient had grade 2 interstitial lung disease (ILD) until the cutoff date. 6 or 7.5mg/kg was selected for dose expansion. Objective response rate (ORR) per RECIST v1.1 was 41.2% (68 partial responses [PR]) in 165 responses evaluable pts who had ≥1 response assessment. Surprisingly, 7 pts reached PR in 10 HER2+ MBC pts with brain metastases, one of whom the brain metastatic lesions reached complete response after 4 cycles of treatment. This trial is ongoing now. Conclusions: TQB2102 is well tolerated with promising anti-tumor activity in pts with HER2-expressing cancer. These early signs of activity support a phase 3 trial in patients with HER2-low MBC that has been initiated (NCT06561607). Clinical trial information: NCT05735496 . 6mg/kg and above ORR(%) DCR(%) 6-months PFS rate, (%) HER2 positive MBC (N=39) 51.3 84.7 87.0 HER2 low MBC (N=33) 51.5 87.9 63.0 HER2 3+ colorectal cancer (N=23) 34.8 87.0 88.4 HER2 positive gastric cancer (N=10) 70.0 90.0 90.0 HER2 positive Other (N=5) 60.0 100.0 NE