MSB2311 is a novel pH-dependent humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody. This phase I study primarily aimed to determine the maximum tolerated dose (MTD)/recommended phase 2 dose level (RP2D) of MSB2311 in patients with advanced solid tumors or lymphoma. MSB2311 was intravenously administered at 3, 10, and 20 mg/kg every 3 weeks (Q3W) and 10 mg/kg every 2 weeks (Q2W) using 3 + 3 design. During expansion phase, eligible patients with either PD-L1 overexpression, Epstein-Barr Virus positive, microsatellite instability high/mismatch repair deficient, or high tumor mutation burden tumors were treated at RP2D. A total of 37 Chinese patients were treated, including 31 with solid tumors and 6 lymphoma. No dose limiting toxicity was reported and MTD was not reached. The trial was expanded at 20 mg/kg Q3W or 10 mg/kg Q2W, both of which were determined as RP2D. Most common drug-related treatment-emergent adverse events were anemia (43.2

TPS375 Background: In normal conditions, Claudin (CLDN)18.2 is a tight junction protein with expression strictly confined to differentiated epithelial cells in gastric mucosa. CLDN18.2 has been found to be upregulated, and involved in tumor development and progression in a variety of tumor types such as gastric, pancreatic, and bile duct cancer (BTC). The biological characteristics of CLDN18.2 suggest it is an ideal therapeutic target for cancer drug development. IMAB362 is the first anti-CLDN18.2 monoclonal antibody (mAb) of high potency to have been tested in humans and it revealed clinical efficacy in gastric cancer in a phase II study. TST001, a humanized IgG1 mAb, binds to a distinct epitope of CLDN18.2 with higher affinity and mediates CLDN18.2 expressing cancer cell death through antibody-dependent cellular cytotoxicity (ADCC) in comparison with IMAB362; Furthermore, TST001 is produced using an optimized glycoengineering process to increase affinity to FcR. The enhanced binding to CLDN18.2 on tumor cells and FcR on NK cells results in more efficient engagement of the tumor cells with NK cells and antibody mediated cellular cytotoxicity. In preclinical xenograft studies, TST001 displayed potent anti-tumor activities in the tumor models with medium to high level of CLDN18.2 expression and synergy anti-cancer effect with checkpoint inhibitor. A mAb specific for CLDN18.2 was also developed as an IHC based biomarker for patient enrollment in the clinical trials. Methods: This is an open-label, multi-center, phase I clinical trial to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK) profile and preliminary anti-cancer effect of TST001 in patients with locally advanced or metastatic solid tumors. (NCT04396821) The study consists of two parts: Part A is a 3+3 dose escalation design with sequential dose cohorts of 1, 3, 6, 10mg/kg in Q2W and Q3W schedules. Based on the emerging safety data, higher doses may be proposed for testing. About 27-54 patients will be enrolled. Dose expansion (Part B) will utilize doses of TST001 based on the emerging data from Part A. In Part B, up to 20 patients with CLDN18.2 overexpression per tumor specific cohort will be enrolled to 3 cohorts: A: TST001 single agent in gastric/gastroesophageal junction (G/GEJ) cancer; B: TST001 + nivolumab in G/GEJ cancer; C: TST001 single agent in pancreatic cancer or BTC. All patients in Part B will be selected by CLDN18.2 expression by central lab testing. The safety, anti-tumor activity, and PK will be further assessed in Part B. Enrolment began in July 2020 in the USA and is ongoing in multiple sites. As of 20 September, 2021, 23 subjects were dosed in Part A and the dose of 10mg/kg is being tested. Another phase I study of TST001 single agent and in combination with chemotherapy in patients with metastatic solid tumor is also ongoing in China (NCT04495296).

3023 Background: MSB0254 is a humanized vascular endothelial growth factor receptor 2 (VEGFR-2) monoclonal antibody. MSB0254 inhibits angiogenesis induced by either VEGF-A or –C. This trial is a phase I study to evaluate MSB0254’s safety, tolerability and PK profiles, as well as early anti-cancer activities in Chinese patients with advanced solid tumors. Methods: In this phase I study (NCT04381325), locally advanced or metastatic solid tumor patients failed previous standard treatments were enrolled. In the dose escalation phase, following 3+3 rules, MSB0254 was given intravenously Q2W (every 2 weeks) at 4mg/kg, 8mg/kg, 12mg/kg, 16mg/kg, and Q3W at 20mg/kg. In the dose expansion phase, patients with selected tumor types will be treated with MSB0254 at 16mg/kg Q2W or 20mg/kg Q3W. Primary objectives were to evaluate the safety and tolerability and to identify maximum tolerable dose (MTD) and/or Recommended Phase 2 Dose (RP2D). Secondary objectives included the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1. Results: As of 10th Jan, 2022, a total of 22 Chinese patients have been enrolled into the dose escalation phase and treated with MSB0254 at different dose levels from 4-16mg/kg Q2W or 20mg/kg Q3W. MTD was not reached. One DLT was reported in 12mg/kg Q2W dose cohort. A subject with intra-cholangial carcinoma developed G3 (grade 3) upper gastrointestinal hemorrhage on the C1D13. The adverse event was resolved after symptomatic treatment. The most common treatment-emergent adverse events (TEAEs) (>10%) included: hypertension (27.3%), AST increased (27.3%), γ-GGT increased (22.7%), neutrophil count decreased (18.2%), proteinuria (18.2%), WBC count decreased (13.6%), platelet count decreased (13.6%) and anemia (13.6%). Three subjects (13.6%) experienced G3 TEAEs: 1 upper gastrointestinal hemorrhage, 1 anemia and 1 Hypertriglyceridemia. No G4/5 TEAE was observed. And three subjects (13.6%) experienced 3 SAEs: 1 upper gastrointestinal hemorrhage, 1 G2 intestinal obstruction caused hospitalization and 1 G2 fatigue caused hospitalization. MSB0254 displayed a dose proportional pharmacokinetic profile between 4-16 mg/kg Q2W with calculated T1/2 of 6-9 days. Eighteen subjects had at least one tumor assessment per RECIST 1.1 after MSB0254 treatment. Eleven subjects (61.1%) had best response of stable disease (SD). Four of them had stable disease for more than 6 months, including a neuroendocrine tumor (NET), a gastric cancer, an epithelioid hemangioendothelioma (EHE) and a submaxillary gland carcinoma patient. Conclusions: MSB0254 demonstrated a manageable safety profile and preliminary antitumor activity in patients with advanced solid tumors. 16mk/kg Q2W is recommended as RP2D. 20mg/kg Q3W is still under investigation. The study of MSB0254 on the expansion phase in selected tumor patients is ongoing. Clinical trial information: NCT04381325.

4062 Background: TST001 is a recombinant humanized IgG1 antibody specifically against human Claudin 18.2 (CLDN18.2) with high affinity and enhanced FcR engaging of NK cells, which can induce strong antibody-dependent cellular cytotoxicity (ADCC) activities. TST001 monotherapy dose-escalation study has been completed (IGCC2022-ABS-1152) and promising anti-tumor activities were observed in advanced gastric cancer patients with CLDN18.2 overexpression who had failed multiple lines of prior therapies. The current study is an open-label, multi-center, multiple cohorts, phase I clinical trial of TST001 monotherapy or in combination with standard treatments in Chinese patients with advanced or metastatic solid tumors (NCT04495296). Methods: This cohort is aimed to determine the recommended phase II dose, evaluate safety, tolerability and preliminary efficacy of TST001 in combination with CAPOX as a 1st line treatment of advanced G/GEJ cancer. A 3+3 design was utilized in the dose escalation phase with treatment naïve advanced G/GEJ cancer patients regardless of Claudin18.2 expression. Claudin 18.2 positive G/GEJ cancer patients were planned to be enrolled in the dose expansion phase in selected dose cohorts. Results: The TST001/CAPOX combination cohort was initiated in August 2021 and is ongoing in multiple sites in China with a data cutoff date of January 27, 2022. 12 subjects were dosed with TST001 with a dose range from 1 to 8mg/kg Q3W in combination with the standard dose of CAPOX in the dose escalation phase and one subject with central lab tested Claudin 18.2 overexpression was dosed in the expansion phase of TST001 at 6mg/kg Q3W with CAPOX. There was no subject experienced dose-limiting toxicity. Treatment-emergent adverse events (TEAEs) were mostly grade 1-2, including nausea (76.9%), anemia (69.2%), vomiting, AST increased (63.8% respectively), hypoalbuminemia, ALT increased (46.2%, respectively). Treatment related grade 3 AEs were hypertension （15.4%）, anemia, hypoproteinemia, WBC count decreased, hypocalcemia aggravated (7.7%, respectively). Among the eight patients from the dose escalation part (with no CLDN18.2 expression selection yet with measurable disease ) with at least one post-treatment tumor assessment, four had achieved partial response, three had achieved stable disease and one had progressive disease as the best tumor response per RECIST1.1. Conclusions: Conclusion: TST001 in combination with CAPOX in first line gastric cancer patients is safe and encouraging anti-tumor activities have been observed. Additional data from the 6 mg/kg dose expansion cohort will be updated at the meeting. Clinical trial information: NCT04495296.

e14547 Background: MSB2311 is a novel humanized PD-L1 antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. Methods: Patients with metastatic solid tumors or selected lymphoma progressed on or after standard treatments were enrolled in this phase I study. In dose escalation part, MSB2311 was given at dose levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, including EBV+, PD-L1+ (TPS≥50%), MSI-High or TMB-High (≥10muts/Mb), were dosed at 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD and RP2D. Secondary objectives include the assessment of pharmacokinetic parameter, immunogenicity, and preliminary anti-cancer activity per RECIST1.1. Results: As of data cutoff by Aug 31, 2020, 33 Chinese patients had been treated, including 27 heavily pre-treated solid tumor patients and 6 lymphoma patients. No dose limiting toxicity was reported and MTD has not been reached. The most common AEs (>20%) included: anemia, hypothyroidism, aspartate aminotransferase elevated, proteinuria, weight loss. 13 patients (39.4%) experienced grade 3 AEs, and 6 patients (18.2%) experienced SAEs. No treatment related grade 4 or 5 event was reported. Of the 17 efficacy evaluable solid tumor patients with biomarker selection, 6 achieved confirmed partial response with 35% ORR: 2/8 (25%) at 10 mg/kg Q2W and 4/9 (44%) at 20 mg/kg Q3W. Additionally, one patient achieved sustained iPR via iRECIST. 4 out of 7 responding patients (including one iPR) achieved tumor shrinkage of more than 50%, 3 of them got durable response (≥24 weeks).1 out of 6 lymphoma patients achieved PR. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and selected lymphomas. Clinical trial information: NCT04272944.

e15011 Background: MSB2311 is a novel humanized programmed death-ligand 1 (PD-L1) antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. Methods: Patients with metastatic solid tumors and selected hematological malignancies progressed after standard treatments were enrolled in this Phase I study. In dose escalation part, MSB2311 was given at levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, either EBV positive, PD-L1 positive, MSI-High or TMB-High, were enrolled and dosed either in 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD/MAD and RP2D. Secondary objectives include the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1. Results: At data cut-off at Jan 19, 2020, 27 Chinese patients have been treated, 18 (66.7%) of them received at least 4 cycles of MSB2311. No dose limiting toxicity was reported and MTD has not been identified. The most common treatment-emergent adverse events (TEAEs) ( > 10%) included: anemia, hypothyroidism, hyperglycemia, hypertriglyceridemia, nausea, vomiting, fatigue, malaise, pyrexia and cough. Eleven patients (40.7%) experienced Grade 3 TEAEs, and 6 patients (22.2%) experienced SAEs. One lymphoma patient experienced grade 4 hypercalcemia and platelet count decreased, which were assessed as related to study drug by the investigator. MSB2311 displayed a linear pharmacokinetic profile with calculated T1/2 of about 10-13 days. Among 18 evaluable patients treated with 20 mg/kg Q3W, the best response of PR was observed in 4 out of 12 patients with solid tumors including NSCLC, NPC and Gastric cancer, and 1 out of 6 patients with lymphoma. The mean duration of response was 127 (range 38-278) days. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and hematological malignancies.