Background: HLX07 is a novel humanized anti-EGFR monoclonal antibody. This study aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HLX07 combined with different chemotherapy regimens (chemo-regimens) in patients with advanced solid tumors. Methods: This was a single-center, open-label, dose-escalation phase 1b/2 study. Three fixed-dose chemo-regimens were given together with HLX07: 1) gemcitabine 1000 mg/m² (on Days 1 and 8) and cisplatin 75 mg/m² (on Day 1) in 3-week cycles for 4–6 cycles; 2) paclitaxel 80 mg/m² and carboplatin AUC = 2 (both on Days 1, 8, and 15) in 3-week cycles for 4–6 cycles; and 3) mFOLFOX6 (on Day 1) in 2-week cycles for 6–12 cycles. Patients with metastatic or recurrent advanced solid tumors suitable to be treated with the above chemo-regimens were given HLX07 IV at escalating doses (400, 600, or 800 mg, QW) combined with chemotherapies following BOIN design. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints included safety and preliminary efficacy. Results: As of August 28, 2022, 56 patients were enrolled; 21 received HLX07 with gemcitabine and cisplatin, 21 received HLX07 with paclitaxel and carboplatin (n = 3 for HLX07 400 and 600 mg, n = 15 for HLX07 800 mg for each chemo-regimen), and 14 received HLX07 with mFOLFOX6 (n = 3 for HLX07 400 and 600 mg, n = 8 for HLX07 800 mg). No DLT related to HLX07 was reported. The MTD was not reached. A summary of treatment-emergent adverse events (TEAEs) in each group is shown in Table 1. All patients experienced TEAEs. Grade ≥3 TEAEs were reported by 17 (81.0%), 20 (95.2%), and 12 (85.7%) patients in each chemo-regimen group, respectively. Only 1 (33.3%) patient in the HLX07 400 mg plus paclitaxel and carboplatin group experienced TEAE leading to death (upper gastrointestinal hemorrhage, possibly unrelated to study drugs). Conclusions: HLX07 was safe and well tolerated when combined with chemotherapy in patients with advance solid tumors. Clinical trial information: NCT03577704.