Carhaix, France

A Phase II Study Evaluating the Efficacy and Safety of XH-S003 Capsules in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NW-301 TCR-T in Patients With Advanced Solid Tumor

this study is an open, two cohorts single infusion, dose escalation/dose regimen finding study to independently assess the safety and pharmacokinetics of KRAS G12V/G12D mutation TCR-T cell therapies, and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumor with KRAS G12V/G12D mutation and failed to standard systemic treatment.

Anti-CD38 Antibody Treating Primary Immune Thrombocytopenia (ITP)

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for recurrent and refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently. The main pathogenesis of ITP is the loss of platelet autoantigen immune tolerance, which leads to abnormal activation of humoral and cellular immunity. It is characterized by antibody mediated platelet destruction and insufficient platelet production by megakaryocytes. The residual long-term autoreactive plasma cells may be a source of therapeutic resistance to autoimmune cytopenia. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. Therefore, the strategy of simply eliminating B cells may not work, because LLPC will continue to produce pathogenic antibodies. However, targeting LLPC becomes a new strategy to treat autoimmune diseases. Daratumumab, a kind of anti-CD38 antibody, is a new type of monoclonal antibody targeting CD38. It targets plasma cells and has carried out some clinical studies in multiple myeloma, with good therapeutic effects. In addition, the clinical trials of daratumumab in the treatment of autoimmune diseases, including membranous nephropathy, systemic lupus erythematosus (SLE) and ITP, are also being carried out simultaneously. The investigators assume that autologous reaction LLPC may be the cause of treatment failure in some ITP patients. Therefore, the use of CD38 monoclonal antibody to clear long-term surviving plasma cells in ITP patients may be a new strategy for treating ITP patients. Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of daratumumab in the treatment of immune thrombocytopenia in patients who are steroid-refractory or steroid-dependent.

A Clinical Study on the Efficacy and Safety of Herombopag in the Treatment of Senile Primary ITP

This is a single-arm, prospective clinical study to evaluate the efficacy and safety of herombopag in the treatment of elderly patients with ITP. The study will include 80 patients. Screening of patients will be 2 weeks after the longest period, to enter after the treatment period, accept the herombopag 5 mg, once daily, on an empty stomach, oral medication can be eating only 2 hours, and 24 weeks of treatment, and adjust the dosage according to the platelet count. If patients do not respond to treatment after 8 weeks, it is recommended to withdraw from the study and continue safety visits for 4 weeks. During treatment, the patient continues treatment until the investigator assesses the occurrence of intolerable toxicity, disease progression, withdrawal of informed consent, or other discontinuation criteria specified in the protocol (whichever occurs first). Follow-up treatment for patients who withdraw from treatment due to safety or ineffectiveness is determined by the investigator according to clinical practice. Safety assessment during treatment, including vital signs, physical examination, laboratory examination, etc.; Check your blood routine at least once a week. A 4-week safety visit was performed after the final treatment.

Efficacy, Safety, Pharmacokinetics of ICP-488 in Patients With Moderate to Severe Plaque Psoriasis

BCMA CAR-T for Dynamic High-risk Multiple Myeloma

The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of BCMA CAR-T in dynamic high-risk patients with multiple myeloma. Patients received BCMA CAR-T cells infusion after standard FC lymphoma deletion therapy.

Study of PN20 in Adult Patients with Primary Immune Thrombocytopenia (ITP)

This is a multicenter, open-label, single-arm, dose-escalation Phase1b study aimed at evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of a single dose of PN20 in adult patients with primary immune thrombocytopenia (ITP). The trial is a dose escalation study, including Screening (no more than 14 days), Treatment (single dose) and the post-treatment follow-up (4 weeks). And the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of PN20 in ITP will be assessed in this study.

Modified Tumor-free Techniques Operation to Cervical Cancer

A progress report will be conducted within 4 weeks after all participants have completed their 6-month postoperative visit (the 5th visit). The report will be performed by an independent third-party statistical team, which will provide a comprehensive analysis of the safety data, baseline characteristic, and perioperative indicators. The study will perform one final analysis.

To Evaluate the Clinical Study of GS1191-0445 Injection in the Treatment of Hemophilia A

A Multicenter, Prospective, Cohort Study of Trop-2 ADC Combination Therapy for Advanced Triple-negative Breast Cancer

1. Study Population - Eligible Participants: Patients with triple - negative metastatic breast cancer at the second line of treatment or higher. Triple - negative invasive breast cancer is histologically confirmed, defined as immunohistochemical detection revealing estrogen receptor (ER) < 10%, progesterone receptor (PR) < 10%, and HER2 0 - 1+ or HER2 2+ with negative fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) results, in accordance with the 2018 ASCO - CAP HER2 - negative identification guidelines. 2. Experimental Design - Study Type: Multicenter, prospective cohort study. 3. Sample Size Determination - The sample size is calculated based on the primary endpoint of progression - free survival (PFS). Drawing on data from ASCENT (a confirmatory phase III study on the efficacy in triple - negative breast cancer) and EVER - 132 - 001 (a Chinese population bridging study presented at the ESMO Congress), the PFS of sacituzumab govitecan monotherapy in metastatic triple - negative breast cancer (mTNBC) is approximately 5.6 months. - Assuming a hazard ratio of 0.70 in each cohort (median PFS value of 8 months vs. 5.6 months), to detect a statistically significant difference between the trial group and the sacituzumab govitecan monotherapy control group at a one - sided significance level of 0.05 and a power of 80%, 51 PFS events are required. Given an enrollment period of 18 months and a total study duration of 30 months, 69 subjects are needed for each cohort. 4. Dosage Regimens - 4.1 Sacituzumab Govitecan Dose and Administration: The recommended dose is 10 mg/kg. It is administered by intravenous infusion on days 1 and 8 of each treatment cycle, with each cycle lasting three weeks. - 4.2 Toripalimab Dose and Administration: 240 mg is administered by intravenous infusion on day 1 of each cycle. Each treatment cycle has a duration of three weeks. - 4.3 Antiangiogenic Targeted Drugs Options and Dosage: Bevacizumab or Anlotinib can be selected. Treatment is carried out according to the standard dosage for each respective drug. 5. Inclusion Criteria - Age between 18 and 70 years. - Histologically - confirmed triple - negative invasive breast cancer as per the defined immunohistochemical and molecular criteria. - For patients with locally advanced or metastatic breast cancer: Those who have undergone radical surgery. Those who have received at least one but no more than two lines of chemotherapy in the advanced treatment phase. Additionally, early - stage triple - negative breast cancer patients who experienced disease progression within one year after neoadjuvant or adjuvant therapy are eligible. - No prior use of immunotherapeutic drugs or anti - angiogenic drugs. - At least one measurable lesion as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. - No contraindications to chemotherapy, immunotherapy, or anti - angiogenic therapy. - Permitted to have stable or asymptomatic brain metastases. - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 2, with a predicted survival exceeding 12 weeks. - All acute toxicities from previous anticancer therapies must have resolved to Grade ≤1 according to the protocol criteria (excluding alopecia) before screening. - Women of childbearing potential must agree to use medically approved contraception during treatment and for at least three months post - treatment. - Adequate organ function meeting the following criteria: Hemoglobin ≥ 90 g/L without transfusion within 14 days. Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L. Platelets ≥ 75×10⁹/L. Total Bilirubin ≤ 1.5× the upper limit of normal (ULN). Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3×ULN (≤ 5×ULN if liver metastasis is present). Serum Creatinine ≤ 1×ULN. Left Ventricular Ejection Fraction (LVEF) ≥ 50%. - Participants must voluntarily enroll in the study, demonstrate excellent adherence, and actively participate in safety and survival follow - up assessments. 6. Exclusion Criteria - Uncontrolled central nervous system metastases (symptomatic or requiring glucocorticoids or mannitol for symptom management). - Symptomatic third - space effusions, including pericardial, pleural, and peritoneal effusions, that cannot be adequately managed by drainage or other therapeutic interventions. - Participation in another clinical trial within 30 days prior to enrollment. History of other malignancies within the past 5 years, excluding adequately treated cervical carcinoma in situ, skin squamous cell carcinoma, thyroid carcinoma, or controlled basal cell carcinoma. - Uncontrolled cardiac conditions, including: - Heart failure classified as NYHA class II or higher. - Unstable angina. - Myocardial infarction within the past year. - Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention. - QTc interval greater than 470 ms. - Arterial or venous thrombotic events within 24 weeks preceding informed consent, such as cerebrovascular accidents (e.g., transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism. - Within 24 weeks prior to signing the informed consent form (ICF), a history of any of the following conditions: peptic ulcer, gastrointestinal perforation, corrosive esophagitis or gastritis, inflammatory bowel disease, diverticulitis, abdominal fistula, tracheoesophageal fistula, or intra - abdominal abscess. Presence of factors that significantly impair oral drug absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction. - Documented history of allergy with potential hypersensitivity or intolerance to sacituzumab govitecan, toripalimab, bevacizumab, or anlotinib. - Active human immunodeficiency virus (HIV) infection, active hepatitis B (hepatitis B surface antigen positive and HBV DNA ≥ 500 IU/ml), or hepatitis C (hepatitis C antibody positive and detectable HCV RNA). - Pregnant women, lactating women, fertile women with a positive baseline pregnancy test, or women of childbearing age who are unwilling to use effective contraception for the duration of the trial. - Presence of concomitant diseases (e.g., poorly controlled hypertension, severe diabetes, neurological or psychiatric disorders) or any other condition that, in the investigator's judgment, could compromise subject safety, confound study results, or prevent subjects from completing the study. 7. Efficacy Endpoints - 7.1 Primary Endpoint Progression - free survival (PFS). - 7.2 Secondary Endpoints Objective response rate (ORR). Overall survival (OS). Safety evaluation. Duration of response (DOR). Clinical benefit rate (DCR). Biomarker studies. - Efficacy is evaluated every two cycles. For treatments showing effectiveness (at least 4 to 6 cycles), immunotherapy or targeted therapy can be continued. 8. Safety Indicators - Adverse events are recorded from the time of completion or signing of the informed consent until the end of the study period as determined by the researchers. All adverse events occurring during this period are to be documented. 9. Statistical Methods - 9.1 General Data Summarization：Unless otherwise specified, data will be summarized using descriptive statistical methods. For measurement data, the mean, standard deviation, median, maximum, and minimum values will be reported. For count data, frequencies and percentages will be used for summarization. - 9.2 Survival Analysis：The Kaplan - Meier method will be employed to estimate survival rates and plot survival curves for time - to - event data, such as PFS and DOR. - 9.3 Blood Concentration Data：Blood concentration data will be summarized using the geometric mean, geometric standard deviation, geometric coefficient of variation, mean, standard deviation, coefficient of variation, median, maximum, and minimum values. - 9.4 Effectiveness Analysis： Effectiveness analysis will be based on the full analysis set (FAS) and the per - protocol set (PPS).The objective response rate (ORR) will be descriptively statistically analyzed according to the stage and dose groups. The number and proportion of subjects with a response (complete response (CR)+partial response (PR)) will be provided, and a two - sided 95% exact confidence interval for the overall ORR will be estimated.PFS and DOR, being time - to - event data, will be analyzed using the Kaplan - Meier method to plot survival curves and estimate the median survival time. When necessary, the two - sided 95% confidence interval for the overall median survival time will be estimated.The clinical benefit rate (DCR) will provide the number and proportion of subjects identified as CR + PR+stable disease (SD), and when necessary, a two - sided 95% exact confidence interval for the DCR will be estimated. - 9.5 Safety Analysis：Safety analysis will be based on the safety set (actual drug categories). It is limited to summary descriptive statistics.