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

January 23, 2024 updated by: Zhejiang Doer Biologics Co., Ltd.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

94

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Senior Clinical Operations Director
  • Phone Number: +86 151 9440 2868
  • Email: yg@doerbio.com

Study Contact Backup

  • Name: Chief Operating Officer
  • Phone Number: +86 05 71 28 25 62 06
  • Email: yf@doerbio.com

Study Locations

  • China
    • Zhejiang
      • Hanzhou, Zhejiang, China, 311100
        • Recruiting
        • Sir Run Run Shaw Hospital,ZheJiang University School Of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DR30303
DR30303 injection treatment. This phase 1 trial will include two stages, a dose escalation stage and an expansion stage.
Drug: DR30303
DR30303 dose level of escalation IV every 3 weeks (Q3W) Day 1, as well as dose expansion with recommended dose level from dose escalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1：Incidence of dose limiting toxicities (DLTs)
Time Frame: up to 21 days following first dose
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
Time Frame: up to 28 days following last dose
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
Time Frame: from date of last dose until the date of will receive DR30303 for 1 year or last documented progression，whichever occurs first
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
Time Frame: 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
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
Time Frame: up to 28 days following last dose
up to 28 days following last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: 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)
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
Disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: 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)
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
Duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: 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)
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
Clinical Benefit Rate
Time Frame: 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
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
Duration of disease control (DDC) per RECIST v1.1
Time Frame: 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)
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
Progression free survival (PFS) per RECIST v1.1
Time Frame: 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
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
6-month and 12-month survival rates
Time Frame: from date of first dose start until the date of first documented progression , 6 months，12 months whichever came first
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
Time Frame: 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
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
Pharmacokinetic (PK) of DR30303: Maximum serum concentration (Cmax)
Time Frame: up to 28 days following last dose
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)
Time Frame: up to 28 days following last dose
up to 28 days following last dose
PK of DR30303: Area Under the concentration-time Curve from time zero to infinity (AUC0-inf)
Time Frame: up to 28 days following last dose
up to 28 days following last dose
PK of DR30303: Time of the maximum concentration (tmax)
Time Frame: up to 28 days following last dose
up to 28 days following last dose
PK of DR30303: Terminal elimination half-life (t1/2)
Time Frame: up to 28 days following last dose
up to 28 days following last dose
Immunogenicity by measurement of Incidence of anti-drug antibodies (ADA)
Time Frame: up to 28 days following last dose
up to 28 days following last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhejiang Doer Biologics Co., Ltd.

Investigators

  • Principal Investigator: Hongming Pan, MD,PhD, Sir Run Run Shaw Hospital
  • Study Chair: Yanshan Huang, PhD, Zhejiang Doer Biologics Co., Ltd.
  • Study Director: Junfang Xu, MD, Huadong Medicine Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 13, 2022

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

November 8, 2022

First Submitted That Met QC Criteria

November 24, 2022

First Posted (Actual)

December 6, 2022

Study Record Updates

Last Update Posted (Estimated)

January 25, 2024

Last Update Submitted That Met QC Criteria

January 23, 2024

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DR30303-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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