Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14-valent recombinant human papillomavirus vaccine.

A novel virus-like particle (VLP)-based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV-type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus-based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen-specific antibody levels need be determined, PBNA is, for many reasons, challenging and time-consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP-microspheres and PE-mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14-valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.

Safety, pharmacokinetics and efficacy of SCT200, an anti-EGFR monoclonal antibody in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer: a phase I dose-escalation and dose-expansion study.

BACKGROUND: An over-expression of the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer and is associated with aggressive disease and poor prognosis. SCT200 is a newly developed recombinant, fully humanized, anti-EGFR monoclonal antibody. This study aimed to evaluate its safety, tolerability, pharmacokinetics (PK), and efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer (mCRC).  METHODS: This phase I study comprising dose-escalation phase and dose-expansion phase. SCT200 was administrated intravenously to groups of three to six patients. An every 3-week dosing cycle (0.5-15.0 mg/kg) and multiple dosing schedule were evaluated. Blood samples were collected at preset intervals for PK assessment, radiological imaging was used for efficacy assessment, and continuous safety monitoring was performed in each group during the study.  RESULTS: From December 16, 2014 to December 31, 2018, fifty-six patients with wild-type KRAS/NRAS/BRAF mCRC receiving ≥ 1 dose of SCT200 were evaluated. Among them, 44.6% (25/56) of the patients failed at least two prior lines of chemotherapy. No dose-limiting toxicities occurred in any group. All of the patients experienced treatment-emergent adverse events (TEAEs). 96.4% (54/56) of patients experienced treatment-related adverse events (TRAEs), and 26.8% (15/56) of patients with Grade ≥ 3 TRAEs. No serious TRAEs were observed. The most common TRAEs were dermotoxicity and hypomagnesemia. PK analysis showed non-linear PK in the range of 0.5 - 8.0 mg/kg of single dose SCT200, the clearance decreased, and the elimination half-life (T1/2) prolonged following dose increase. In the multiple-dose period, the clearance decreased, peak concentration increased, and T1/2 prolonged during prolonged drug administration, and a steady state was reached after five consecutive dose of 6.0 mg/kg quaque week (QW). The objective response rate (ORR) was 30.4% (17/56, 95% confidence interval [CI], 18.8%-44.1%). The ORR in the dose-expansion group (6.0 mg/kg QW) was 48.0% (12/25, 95% CI, 27.8%-68.7%), the median progression-free survival was 5.2 months (95%CI, 3.6-5.5), and the median overall survival was 20.2 months (95%CI, 12.1-not reached). CONCLUSIONS: SCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov ( NCT02211443 ).

Comparison of efficacy and safety of ripertamab (SCT400) versus rituximab (Mabthera® ) in combination with CHOP in patients with previously untreated CD20-positive diffuse large B-cell lymphoma: A randomized, single-blind, phase III clinical trial.

This study compared the efficacy, safety and immunogenicity of ripertamab (SCT400) and rituximab (Mabthera® ) combined with CHOP as the first-line treatment for Chinese patients with CD20-positive diffuse large B cell lymphoma (DLBCL). This is a randomized, patient-blind, multicenter, active-control, non-inferiority study with parallel design. Patients were randomly (2:1) to receive ripertamab combined with CHOP (S-CHOP) or rituximab (Mabthera® ) combined with CHOP (R-CHOP) for up to 6 cycles. The primary endpoint was the Independent Review Committee (IRC) assessed objective response rate (ORR) in full analysis set (FAS) and the per protocol set (PPS). A total of 364 patients (243 in the S-CHOP and 121 in the R-CHOP groups) were enrolled in this study. In FAS, IRC-assessed ORRs were 93.8% (95% confidence interval (CI) 90.0%, 96.5%) and 94.2% (95% CI: 88.4%, 97.6%) in the S-CHOP and R-CHOP groups (p = 0.9633), respectively. The ORR difference between the two groups -0.4% (95% CI: -5.5%, 4.8%) met the pre-specified non-inferiority margin of -12%. There were no significant differences between the S-CHOP and R-CHOP groups in 1-year progression-free survival rates (81.1% vs. 83.2%, p = 0.8283), 1 year event-free survival rates (56.2% vs. 58.1%, p = 0.8005), and 3-year overall survival rates (81.0% vs. 82.8%, p = 0.7183). The results in PPS were consistent with those in FAS. The rates of treatment-emergent adverse events (TEAEs) and ≥ grade 3 TEAEs were 97.9% and 99.2%, 85.2% and 86.0% in the S-CHOP and R-CHOP groups, respectively in safety set. The percentage of anti-drug antibodies positive patients in the S-CHOP group was numerically lower than the R-CHOP group (10.9% vs. 16.0%). This study demonstrated that S-CHOP was not inferior to R-CHOP in the first-line treatment of Chinese patients with CD20-positive DLBCL in efficacy, safety and immunogenecity. S-CHOP could be an alternative first-line standard treatment regimen for this patient population.

Efficacy, safety and pharmacokinetics of recombinant human coagulation factor VIII (omfiloctocog alfa) in previously treated Chinese children with severe hemophilia A.

INTRODUCTION: Omfiloctocog alfa, the first China-developed recombinant factor VIII (FVIII), demonstrated efficacy and safety of prophylaxis in previously treated patients (PTPs) aged ≥12 years with severe hemophilia A in China. AIMS: To investigate efficacy, safety and pharmacokinetics (PK) of omfiloctocog alfa in pediatric PTPs with severe hemophilia A in China. METHODS: PTPs (>50 exposure days [ED] for Chinese patients aged <6 years; >150 EDs for patients aged 6-12 years) were treated with omfiloctocog alfa at 25-50 IU/kg every other day or three times per week for 24 weeks. PK was evaluated after single injection of 50 IU/kg. The primary efficacy endpoint was annualized bleeding rate (ABR). RESULTS: A total of 69 patients were enrolled (<6 years, n = 35; 6-12 years, n = 34) and mean exposure to omfiloctocog alfa was 78.9 days. Mean half-life was 6.7 and 10.2 h in children < 6 years and 6-12 years, respectively. Estimated mean ABRs of all patients were 4.05 for overall bleeding episodes and 1.38 for spontaneous bleeding episodes. Of 127 bleeding episodes, the success rate was 92.1%. 39.7% patients did not experience any bleeding episodes and the mean weekly dose of FVIII was 109.1 IU/kg for these patients. 83% bleeding episodes were controlled with ≤2 injections. Adverse reactions occurred in 2.9% of the patients. One 2-year-old patient developed inhibitors after 12 EDs and it resolved with omfiloctocog alfa immune tolerance induction. CONCLUSION: Omfiloctocog alfa was efficacious and well tolerated for the prevention and treatment of bleeding in Chinese pediatric PTPs with severe hemophilia A.

A multi-center, open-label, randomized, parallel-controlled phase II study comparing pharmacokinetic, pharmacodynamics and safety of ripertamab (SCT400) to rituximab (MabThera®) in patients with CD20-positive B-cell non-Hodgkin lymphoma.

Objective: This multi-center, open-label, randomized, parallel-controlled phase II study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD) and safety profile of ripertamab (SCT400), a recombinant anti-CD20 monoclonal antibody, to rituximab (MabThera®) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL). Methods: Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab (375 mg/m2) or rituximab (MabThera®, 375 mg/m2). PK was evaluated using area under the concentration-time curve (AUC) from time 0 to d 85 (AUC0-85 d), AUC from time 0 to week 1 (AUC0-1 w), AUC from time 0 to week 2 (AUC0-2 w), AUC from time 0 to week 3 (AUC0-3 w), AUC from time 0 to week 8 (AUC0-8 w), maximum serum concentration (Cmax), terminal half-life (T1/2), time to maximum serum concentration (Tmax) and clearance (CL). Bioequivalence was confirmed if the 90% confidence interval (90% CI) of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%. PD, immunogenicity, and safety were also evaluated. Results: From December 30, 2014 to November 24, 2015, a total of 84 patients were randomized (ripertamab, n=42; rituximab, n=42) and the PK analysis was performed on 76 patients (ripertamab, n=38; rituximab, n=38). The geometric mean ratios of ripertamab/rituximab for AUC0-85 d, AUC0-inf, and Cmax were 96.1% (90% CI: 87.6%-105.5%), 95.9% (90% CI: 86.5%-106.4%) and 97.4% (90% CI: 91.6%-103.6%), respectively. All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%. For PD and safety evaluation, there was no statistical difference in peripheral CD19-positive B-cell counts and CD20-positive B-cell counts at each visit, and no difference in the incidence of anti-drug antibodies was observed between the two groups. The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups. Conclusions: In this study, the PK, PD, immunogenicity, and safety profile of ripertamab (SCT400) were similar to rituximab (MabThera®) in Chinese patients with CD20-positive B-cell NHL.

Pharmacokinetic, efficacy and safety evaluation of B-domain-deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A.

INTRODUCTION: SCT800 is a recombinant human B-domain-deleted coagulation factor VIII (BDDrFVIII) developed in China. AIM: To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A. METHODS: A phase III, multicentre, prospective, open-label, single-arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed. RESULTS: A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01-3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1-2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment-related adverse events was 53.4%. Drug-related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified. CONCLUSIONS: SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.

Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice.

AIM: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice. METHODS: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1-200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss. RESULTS: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha. CONCLUSION: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma.

OBJECTIVE: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20(+) B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. METHODS: Fifteen patients with CD20(+) B-cell NHL received dose-escalating SCT400 infusions (250 mg/m(2): n=3; 375 mg/m(2): n=9; 500 mg/m(2): n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. RESULTS: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m(2) dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m(2) to 500 mg/m(2), the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. CONCLUSIONS: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20(+) B-cell NHL.

Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase â ¡ study.

BACKGROUND: Limited therapeutic options are available for metastatic colorectal cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet medical need for novel therapies. METHODS: This is an open-label, single arm, multicenter, phase Ⅱ study aiming to perform the efficacy, safety and genomic analysis of SCT200, a noval fully humanized IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type mCRC. SCT200 (6 mg/kg) was given weekly for the first six weeks, followed by a higher dose of 8 mg/kg every two weeks until disease progression or unacceptable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) and secondary endpoints included ORR in patients with left-sided tumor, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. FINDINGS: From February 12, 2018 to December 1, 2019, a total of 110 patients aged between 26 and 77 years (median: 55; interquartile range [IQR]: 47-63) with fluorouracil, oxaliplatin, and irinotecan refractory RAS and BRAF wild-type mCRC were enrolled from 22 hospitals in China. As the data cut-off date on May 15, 2020, the IRC-assessed ORR and DCR was 31% (34/110, 95% confidence interval [CI] 22-40%) and 75% (82/110, 95% CI 65-82%), respectively. Thirty one percent (34/110) patients achieved confirmed partial response (PR). The median PFS and median OS were 5.1 months (95% CI 3.4-5.2) and 16.2 months (95% CI 11.1-not available [NA]), respectively. The most common ≥ grade 3 treatment-related adverse events (TRAEs) were hypomagnesemia (17%, 19/110) and acneiform dermatitis (11%, 12/110). No deaths occurred. Genomic analysis suggested positive association between MYC amplification and patients' response (P = 0.0058). RAS/RAF mutation and MET amplification were the most frequently detected resistance mechanisms. Patients with high circulating tumor DNA (ctDNA) at baseline or without ctDNA clearance at the 7th week after the first dose of SCT200 administration before receiving SCT200 had worse PFS and OS. INTERPRETATION: SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy. FUNDING: This study was sponsored by Sinocelltech Ltd., Beijing, China and partly supported by the National Science and Technology Major Project for Key New Drug Development (2019ZX09732001-006, 2017ZX09304015).

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Safety and immunogenicity of multivalent SARS-CoV-2 protein vaccines: a randomized phase 3 trial.

Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma.

OBJECTIVE: The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies. METHODS: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95% CI: 5.6%-34.7%). The median PFS and OS were 3.1 months (95% CI: 1.5-4.3) and 6.8 months (95% CI: 4.7-10.1), respectively. A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions (≥ 50%: 25.0% vs. < 50%: 0%, P = 0.140) or TP53 mutation abundance (< 10%: 23.8% vs. ≥ 10%: 0%, P = 0.286). Improved median PFS (3.4 vs. 1.4 months, P = 0.006) and OS (8.0 vs. 4.2 months, P = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-related adverse events of grade 3 or 4 (occurring in ≥ 2 patients) were hypomagnesemia [7 (23.3%)] and rash [2 (6.7%)]. No treatment-related death occurred. CONCLUSIONS: SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.