Malignant Neoplasm of Digestive System
Conditions
Keywords
Malignant neoplasm of digestive system
Brief summary
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.
Detailed description
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.
Interventions
DRUGDR30303
DR30303 dose level of escalation IV every 3 weeks (Q3W) Day 1, as well as dose expansion with recommended dose level from dose escalation.
Sponsors
Zhejiang Doer Biologics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1：Incidence of dose limiting toxicities (DLTs) | up to 21 days following first dose |
| Part 1：Number, severity and duration of treatment-emergent adverse events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 | up to 28 days following last dose |
| Part 1：Maximum Tolerated Dose (MTD) and/or Biological effective dose (BED) based on safety, tolerability, PK profile and preliminary efficacy data | from date of last dose until the date of will receive DR30303 for 1 year or last documented progression，whichever occurs first |
| Part 2: Recommended Phase 2 Dose (RP2D) based on safety, tolerability, PK profile, and preliminary efficacy data | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first |
| Part 2: Number, severity and duration of treatment-emergent adverse events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 | up to 28 days following last dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | These measure are defined as the proportion of subjects with complete response (CR) or partial response (PR) |
| Disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | These measure are defined as the proportion of subjects with CR, PR and stable disease (SD) |
| Duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | These measure are defined as the duration from the first occurrence of confirmed CR or PR until the date of disease progression or death (from any cause) |
| Clinical Benefit Rate | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | Defined as Proportion of subjects with CR, PR and duration of SD ≥ 12 weeks |
| Duration of disease control (DDC) per RECIST v1.1 | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | For subjects with CR, PR, or SD, duration was calculated from the first assessment as CR, PR, or SD until the date of disease progression or death (from any cause) |
| Progression free survival (PFS) per RECIST v1.1 | from date of first dose start until the date of first documented progression，or the date of death from any cause, or the date of will receive DR30303 for 1 year whichever came first | These measure are defined as time from start of treatment to tumor progression or death from any cause |
| 6-month and 12-month survival rates | from date of first dose start until the date of first documented progression , 6 months，12 months whichever came first | — |
| Overall survival (OS) per RECIST v1.1 | from date of first dose start until the date of first documented progression or death from any cause，or the date of will receive DR30303 for 1 year whichever came first | These measure are defined as time from start of treatment to death from any cause |
| Pharmacokinetic (PK) of DR30303: Maximum serum concentration (Cmax) | up to 28 days following last dose | — |
| PK of DR30303: Area Under the concentration-time Curve from time zero to the last quantifiable concentration (AUC0-last) | up to 28 days following last dose | — |
| PK of DR30303: Area Under the concentration-time Curve from time zero to infinity (AUC0-inf) | up to 28 days following last dose | — |
| PK of DR30303: Time of the maximum concentration (tmax) | up to 28 days following last dose | — |
| PK of DR30303: Terminal elimination half-life (t1/2) | up to 28 days following last dose | — |
| Immunogenicity by measurement of Incidence of anti-drug antibodies (ADA) | up to 28 days following last dose | — |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORHongming Pan, MD,PhD
Sir Run Run Shaw Hospital
STUDY_CHAIRYanshan Huang, PhD
Zhejiang Doer Biologics Co., Ltd.
STUDY_DIRECTORJunfang Xu, MD
Huadong Medicine Co., Ltd.
Outcome results
None listed