A Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of DR30303 in Patients With Advanced Solid Tumors

An Open, Phase I, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of DR30303 in Patients With Advanced Solid Tumors

This study is an open-label Phase 1, First in Human trial of DR30303, a recombinant humanized monoclonal antibody that targets Claudin18.2 (CLDN18.2). It is composed of humanized variable domain of heavy chain of antibody (VHH) fused with engineered immunoglobulin gamma-1(IgG1) Fc. It is being testing against advanced and/or metastatic solid tumors.

This study is an open, phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of DR30303 in patients with advanced solid tumors. The study is composed of two parts: part 1 is Dose escalation stage and part 2 is Dose expansion stage.

Inclusion Criteria:

1. Fully informed of this study and voluntarily sign informed consent form (ICF).
2. Aged 18 to 75 years, gender is not limited.
3. Part 1: Dose escalation stage - the subject have histologically or cytologically confirmed locally advanced or metastatic malignant solid tumors who have failed or are intolerant to prior systemic therapy.
4. Part 2: Dose expansion stage- CLDN18.2 positive confirmed by central laboratory locally advanced unresectable or metastatic gastric cancer (GC)/gastroesophageal junction (GEJ ) or Pancreatic cancer those who had failed or were intolerant to at least 1 line of systemic therapy.
5. The Eastern Cooperative Oncology Group (ECOG) score is 0 to 1.
6. Expected survival ≥ 3 months.
7. Adequate organ function.
8. Referring to the RECIST 1.1 standard, there is at least one measurable lesion.

Exclusion Criteria:

1. Radical radiotherapy was performed within 12 weeks before the first dose of study drug.
2. Subjects who have received other systemic anti-tumor therapy within 4 weeks before the first dose of study drug.
3. Subjects who received or are scheduled to receive live attenuated vaccine within 4 weeks.
4. Received systemic steroids equivalent to >10mg/d prednisone within 2 weeks before the first dose of study drug, except inhaled steroids.
5. Subjects who have undergone or are expected to undergo major surgery, or have severe unhealed wounds, etc. prior to the first dose of study drug.
6. Ever received any treatments targeting Claudin18.2.
7. Subject who have a history of allergy to any component in the DR30303.
8. Subject with uncontrolled intracranial metastases.
9. Uncontrollable pleural effusion, pericardial effusion and ascites effusion existed before enrollment.
10. hepatitis B virus (HBV), hepatitis C virus (HCV), HIV or syphilis infection.
11. Diseases or associated risks that are judged by the investigator to be inappropriate for enrollment, such as poorly controlled diabetes,etc.
12. Subjects with interstitial lung disease requiring treatment such as oral or intravenous corticosteroids.
13. Subjects with previous or concomitant malignancies, with the following exceptions: non- melanoma skin carcinoma in situ, superficial bladder cancer, etc.
14. Clinically significant cardiovascular and cerebrovascular diseases within 6 months before the first dose of study drug, such as New York Heart Association (NYHA) class III or IV congestive heart failure, etc.
15. Female patients who are breastfeeding.
16. The investigator assesses that the subject is unable or unwilling to comply with the requirements of the research protocol.
17. Participated in other clinical studies within the past 4 Weeks.