DXP-106 in Solid Tumor Patients.

To accurately assess DLT, DLT-evaluable subjects are defined as one who meets any of the following criteria during the DLT evaluation period:

• The patient experiences a DLT at any time after DXP-106 infusion during the DLT observation period.
• The patient completes at least 75% of the planned total dose of DXP-106 infusion during the DLT evaluation period and have fulfilled the safety evaluation requirements during the DLT observation period.

For Part 1 (monotherapy dose escalation) and Part 2 (combination therapy dose escalation) of this study, patients who discontinue prior to completion of the DLT evaluation period in the first cycle after the first dose for reasons other than DLT, or who do not meet any of the above criteria, will be considered non-evaluable for DLT.

Subjects who are not evaluable for DLT due to non-DLT reasons will be replaced, leading to an increase in the actual sample size.

Inclusion criteria

• Participants who fully understand the trial objectives, nature, procedures, and potential adverse reactions, and who voluntarily agree to participate in the study and provide signed informed consent.
• Patients aged 18 to 80 years (inclusive, based on the date of signing the informed consent form), both male and female.
• Measurable disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST criteria within 4 weeks prior to screening.
• Study Population

• Part 1: Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who are ineligible for surgery or curative radiotherapy and have experienced disease progression after standard treatment or are intolerant to such therapy. Target tumor types include but are not limited to colorectal cancer, pancreatic ductal adenocarcinoma (PDAC), head and neck squamous cell carcinoma, lung cancer (LC), Ewing sarcoma (ES), and triple-negative breast cancer (TNBC).
• Part 2: If the participant received adjuvant/neoadjuvant therapy before or after completing prior curative treatment, and the participant's disease has recurred, the interval between the end of adjuvant/neoadjuvant therapy and the first dose in this study must exceed 6 months.

• LC patients: Patients with locally advanced/metastatic lung cancer confirmed by histology or cytology, who relapsed after first-line treatment and must meet the criteria for receiving platinum-based chemotherapy as first-line or second-line standard treatment;
• PDAC Patients: Patients with newly diagnosed histologically or cytologically confirmed, unresectable or radiotherapeutically ineligible locally advanced or metastatic PDAC, who have not received previous treatment and are eligible for standard of care chemotherapy regimens.
• ES patients: Patients with pathologically confirmed unresectable or locally advanced or metastatic Ewing's sarcoma that has failed standard treatment, and a detailed pathological report must be provided. Patients have received at least 1 but no more than 2 lines of systemic therapy previously, and must be eligible for standard chemotherapy regimens.
• TNBC patients (for patients with bilateral breast cancer, both sides must be TNBC): Patients with histologically or cytologically confirmed, inoperable locally advanced or metastatic breast cancer, with ER, PR, and HER-2 all negative. The definition of ER and PR negativity is: IHC ER < 1%, IHC PR < 1%. The definition of HER-2 negativity is: IHC HER-2 (-) or (1+); for those with HER-2 (2+), FISH testing must be performed and the result must be negative. Patients must be eligible for standard chemotherapy regimens;
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
• Life expectancy > 3 months.
• Adequate organ function meeting the following criteria:

• Hematology (without transfusion, hematopoietic growth factors, or medication to correct blood cell counts within 14 days prior to first dose): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 75 × 109/L (part1) or platelet count ≥ 100 × 109/L (part2), hemoglobin ≥ 9.0 g/dL.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) (for patients not receiving anticoagulant therapy); patients on oral anticoagulants with an INR between 2 and 3 were eligible.
• Hepatic function: Total bilirubin (TBIL) ≤ 1.5 × ULN ); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ALT and AST≤ 5.0 × ULN for patients with primary hepatocellular carcinoma (HCC) or hepatic metastases.
• Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance > 50 mL/min (calculated using the Cockcroft-Gault formula).
• Both female and male patients of reproductive potential must have agreed to use reliable contraceptive methods during the trial and for 6 months after the last dose.

Exclusion criteria

• Participants with a history of hypersensitivity, particularly those allergic to the investigational drug or its excipients, or those who have previously experienced severe allergic reactions to macromolecular protein preparations/monoclonal antibodies.
• Participants who have received live/live attenuated vaccines, etanercept or other TNF-α inhibitors, or any other investigational drug during or prior to participation in this study (within 4 weeks before the first dose of the investigational drug or within 5 half-life of the investigational drug, whichever is longer).
• In Part 2, LC patients have received other anti-tumor drug treatments in addition to first-line treatment medications; patients with gene mutations that can be used as targets for targeted therapy (including but not limited to EGFR, ALK, ROS, KRAS) (excluding patients who have progressed on standard targeted therapy and whose next-line standard treatment is a platinum-based dual-drug regimen).
• The toxicity from previous treatments has not alleviated to the level specified in the inclusion/exclusion criteria or to NCI CTCAE ≤ Grade 1 (except for alopecia, pigmentation, Grade 2 peripheral neuropathy, adrenal insufficiency, and other toxicities deemed by the investigator to pose no safety risk to the participant).
• Presence of other active malignancies besides the primary tumor within the past 2 years, with the following exceptions: participants cured with curative-intent therapy and without evidence of recurrence, such as basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder carcinoma, papillary thyroid carcinoma, carcinoma in situ of the cervix, or breast carcinoma in situ.
• History of active autoimmune disease requiring treatment with systemic immunosuppressive agents, or participants requiring systemic immune-related therapy due to immunocompromise from any cause, including but not limited to autoimmune conditions such as systemic lupus erythematosus and active psoriasis.
• Active infection requiring intravenous treatment or unexplained body temperature >38.5°C during the screening period.
• Major surgery within 4 weeks prior to the first dose of the investigational drug.
• Prior cell therapy within 3 months before the first dose of the investigational drug.
• Immunocompromised individuals requiring systemic treatment.
• Participants with significant cardiovascular disease, defined as any of the following:

• Congestive heart failure with New York Heart Association (NYHA) Class ≥ 3; left ventricular ejection fraction (LVEF) < 50%;
• History of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment;
• Malignant arrhythmias requiring pharmacotherapy, second- or third-degree atrioventricular block; congenital long QT syndrome, or prolongation of QT/QTc interval on screening electrocardiogram (QTcF: >450 ms for males and >470 ms for females, calculated using Fridericia's method. If QTc is abnormal, up to 3 consecutive measurements may be obtained at intervals ≤5 minutes and the average value used);
• Uncontrolled hypertension despite pharmacologic management (hypertension inadequately controlled with medications, with systolic blood pressure ≥150 mmHg and diastolic blood pressure ≥100 mmHg);
• Other cardiac abnormalities judged by the investigator to be clinically significant and likely to compromise study safety.
• Presence of severe pulmonary disease at screening, such as pulmonary embolism or interstitial lung disease, with severely impaired pulmonary function as judged by the investigator.
• Newly diagnosed brain metastases or brain metastases with central nervous system symptoms, or other evidence indicating uncontrolled metastases who are considered ineligible per investigator assessment. Participants with leptomeningeal metastases are not recommended for enrollment. Participants with brain metastases may be enrolled if they are clinically stable as assessed by the investigator following treatment and do not require steroid therapy for at least 28 days prior to the first study dose.
• Seropositive for syphilis antibody; positive HIV test; presence of active hepatitis B [Active hepatitis B (HBV) is defined as positive HBsAg or positive HBcAb with HBV DNA greater than the upper limit of the site reference range (i.e., above the lower limit of detection). If HBV DNA is positive (above the lower limit of detection), participants may receive anti-HBV antiviral therapy and may be rescreened. Participants may be enrolled if HBV DNA falls below the lower limit of detection after treatment.] or active hepatitis C [Active hepatitis C is defined as positive HCV RNA (HCV RNA level above the lower limit of detection)].
• History of allogeneic tissue/solid organ transplantation requiring immunosuppressive therapy.
• Patients who experienced immune-related toxicity during prior antitumor immunotherapy and permanently discontinued treatment as a result.
• Severe hereditary or acquired bleeding tendency or coagulation disorder.
• Inability to undergo venipuncture and/or tolerate venous access.
• Pregnant or lactating women.
• Before the first administration of the study drug, the washout period for previous systemic anti-tumor treatments is insufficient, including:

• Chemotherapy < 3 weeks, except for oral fluorouracil (such as tegafur and capecitabine), which requires 2 weeks or within 5 half-lives before the first administration, whichever is shorter;
• Small molecule targeted therapy < 2 weeks or 5 half-lives, whichever is shorter;
• Antibody therapy (including ADC) or biological therapy < 3 weeks;
• Traditional Chinese medicines with anti-tumor indications or non-specific immunomodulators (such as thymosin, interferon, interleukin, and traditional Chinese medicines with clear immunomodulatory indications, etc.) < 2 weeks.
• Definitive radiotherapy < 4 weeks, limited-field local palliative radiotherapy < 2 weeks.
• Endocrine anti-tumor therapy or small-molecule immunotherapy < 2 weeks or 5 half-lives, whichever is shorter.
• Any other condition considered by the investigator as potentially affecting the participant's ability to provide informed consent or comply with the trial protocol, or that may influence the trial results or participant safety.