The goal of this clinical trial is to evaluate the safety and tolerability of DXP-106 in Chinese patients with advanced solid tumors. The main questions it aims to answer are:

For Part I:

1. The safety and tolerability of DXP-106 monotherapy in patients with advanced solid tumors;
2. The dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D);
3. The pharmacokinetics (PK) profile, the immunogenicity of DXP-106 following administration in patients with advanced solid tumors;
4. The preliminary efficacy of DXP-106 in patients with advanced solid tumors;
5. The pharmacodynamic (PD) profiles of DXP-106 following administration in patients with advanced solid tumors as exploratory objective;

For Part2:

1. The safety and tolerability of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors;
2. The recommended dose of DXP-106 in combination with standard of care chemotherapy and/or potential responsive tumor types;
3. The efficacy of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors;
4. The PK profile and immunogenicity of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors;
5. The PD profiles of DXP-106 in combination with standard of care chemotherapy in patients with advanced solid tumors.

The dose escalation is designed with five cohorts, including Cohort 1 (1.0 mg/kg), Cohort 2 (2.0 mg/kg), Cohort 3 (4.0 mg/kg), Cohort 4 (6.0 mg/kg), and Cohort 5 (8.0 mg/kg) in part 1. Each treatment cycle consists of 4 weeks, with administration once weekly (QW) in the first cycle and once every two weeks (Q2W) in subsequent cycles. Treatment will continue until disease progression, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or discontinuation due to other reasons. Based on the continuously obtained data from Part 1 monotherapy dose escalation, the Part 2 combination therapy exploration will be scheduled to commence. The combination therapy dose-escalation is planned to include three dose levels, tentatively designated as Dose Level 1 (DL1), DL2, and DL3 in PDAC patients. Dose escalation will follow the "traditional 3+3" rule, proceeding sequentially from DL1 to DL3. Safety Review Committee (SRC) will determine whether to proceed with escalation to higher doses based on available data, including but not limited to safety, tolerability, PK/PD, and preliminary efficacy. The SRC will discuss and make appropriate decisions when any other unanticipated circumstances occur during the clinical trial.

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

1. The patient experiences a DLT at any time after DXP-106 infusion during the DLT observation period.
2. 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 75 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 ≥ 100 × 109/L, 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) ≤ 3 × ULN.
  • 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 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 of NCI CTCAE ≤ Grade 1 (except for alopecia and pigmentation).

• Presence of other active malignancies besides the primary tumor within the past 5 years. Excluding participants who have been cured through radical treatment, such as basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast, etc.

• History of active autoimmune disease requiring systemic immunosuppressive therapy, including but not limited to systemic lupus erythematosus, psoriasis, etc.

• Active infection requiring treatment or unexplained body temperature >38.5°C during the screening period.

• Major surgery, cytotoxic chemotherapy, immunotherapy, or biologic therapy 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.

• Patients with significant cardiovascular diseases (e.g., congestive heart failure, unstable angina, atrial fibrillation, arrhythmias, uncontrolled hypertension, etc.) : history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment; congestive heart failure classified as New York Heart Association (NYHA) Class ≥ III; left ventricular ejection fraction (LVEF) < 50%; congenital long QT syndrome; or any other clinically significant cardiac condition.

• Presence of severe pulmonary diseases at screening, such as pulmonary embolism or interstitial lung disease.

• Central nervous system (CNS) metastasis or meningeal metastasis with clinical symptoms, or other evidence that such metastases have not been controlled, and the investigator judges it to be unsuitable for inclusion;

• Positive syphilis antibody test; active HIV-related opportunistic infection; active hepatitis B or hepatitis C; Active HBV is defined as positivity for HBsAg or HBcAb with HBV DNA above the central laboratory upper limit of reference (i.e., above the lower limit of detection); participants who are HBsAg-positive or HBcAb-positive but have HBV DNA below the lower limit of detection may be included if they have received stable and effective antiviral therapy for at least 2 weeks prior to enrollment and have normal liver function; Active HCV is defined as positivity for HCV RNA (HCV RNA test result 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;
  • Chinese herbal 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.

• 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.

De-identified individual participant data will be made available to researchers whose proposed research aims are consistent with the study objectives, following publication of the primary results in an ICMJE-approved journal, after approval by the study sponsor/investigator and upon reasonable request.

Mar 2028-Dec 2028

De-identified individual participant data will be accessible to qualified researchers following publication in an ICMJE journal, after review of a research proposal and execution of a data use agreement. Access will be provided via reasonable request to the study sponsor or principal investigator.