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Study of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma

Primary Purpose

Small Cell Lung Cancer, Neuroendocrine Carcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ZG006
Sponsored by
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Fully understand the study and voluntarily sign the informed consent form; Male or female 18~75 years of age; Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), who had no standard treatment available, or were intolerant to standard treatments; Archival tissue sample or fresh biopsy tissue sample must be available for DLL3 detection; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Life expectancy ≥ 3 months; Must have evaluable or measurable lesion. For lesions that have received radiation therapy, only after the progression of the lesions, they can be considered evaluable or measurable lesions; All adverse events from prior treatment have either returned to baseline or CTCAE 5.0 ≤ Grade 1, except for AEs not constituting a safety risk in the opinions of the investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone replacement, etc.; Female and Male patients must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug. Exclusion Criteria: Patients having received any of the following treatments: Anti-DLL3 and anti-CD3 drugs (including investigational drugs); Chemotherapy, biotherapy, endocrine therapy (except for hormone replacement), and biological targeted medicines ≤ 4 weeks before the study entry. Local palliative radiotherapy and a small molecule targeted therapy ≤ 2 weeks (or 5 half-lives, whichever is longer) before the study entry; Systemic immunosuppressive medications, such as corticosteroid (doses > 10 mg/day prednisone or equivalent dose) within 14 days prior to the study entry; Use of any vaccines against viral infections (COVID-19, influenza, varicella, etc.) within 4 weeks of study entry; Received any blood transfusion, EPO, G-CSF, albumin infusion and renal replacement therapy within 14 days prior to study entry. The main organ function meets any of the following criteria within 7 days prior to study entry; Hematological function: ANC < 1.5×10^9/L, PLT < 75×10^9/L, Hemoglobin (Hb) < 100 g/L; Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3×ULN, ALT and AST ≥ 5×ULN for liver metastases patients; Total bilirubin (TBIL) ≥ 1.5×ULN; albumin < 30g/L; Creatinine clearance (Cockcroft-Gault formula) < 50 mL/min; INR > 1.5 or APTT > 1.5×ULN; Medical history, computed tomography (CT) or magnetic resonance imaging (MRI) results indicate the existence of central nervous system (CNS) metastases; Note: Not applicable to the following conditions: subjects with stable CNS metastases; Uncontrollable third cavity effusion (e.g. a large amount of pleural effusion, ascites, or pericardial effusion, etc.) requiring repeated drainage, which was judged by the investigator to be unsuitable for study; Any other malignancy within 5 years (other than radically removed and has not recurred tumors including basal cell skin carcinoma, squamous cell skin carcinoma, superficial bladder cancer, localized prostate cancer, cervical cancer and other cancer in situ, etc.); Severe cardiac-cerebral vascular disease, including but not limited to: Acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or stent implantation within 6 months before study entry; New York Heart Association functional class II to IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50% or the lower limit of normal; Uncontrollable hypertension (even though the best treatment is used but systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg). QTc (F) interval prolonged in electrocardiography during the screening baseline period (> 480 ms) History of autoimmune disease, including but not limited to systemic lupus erythematosus, nephritis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis (except for the following: type I diabetes mellitus, skin diseases that do not require systemic treatment (such as vitiligo), controllable celiac disease, and childhood asthma that completely resolved in adulthood without intervention); Active infection (such as acute bacterial infection, tuberculosis, active hepatitis B/C, active syphilis, or active human immunodeficiency virus infection). Active hepatitis B is defined as: hepatitis B virus DNA titer > 10000 copies/mL or 2000 IU/mL; active hepatitis C is defined as: a positive hepatitis C antibody and HCV viral load above the limit of quantification; active human immunodeficiency virus infection is defined as: antibody positive; Active neurologic paraneoplastic syndrome; Interstitial lung disease or non-infectious pneumonitis (other than radiation-induced pneumonia); Having received prior allogeneic stem cell transplantation or solid organ transplantation; Known allergy to other mAbs or any antibody excipients; the history of a severe allergic reaction, anaphylactoid or other hypersensitivity reactions to humanized antibodies or fusion proteins; Known history of diagnosed neurological or mental disorders, for example, epilepsy, dementia, etc.; A female who is pregnant or nursing; Patients were deemed unsuitable for participating in the study by the investigator for any reason.

Sites / Locations

  • Henan Cancer Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: Dose Escalation

Part 2: Dose Expansion

Arm Description

During the dose-escalation, an accelerated titration design (ATD) will be utilized for the first two dose groups (0.03mg and 0.1 mg), and the conventional "3+3" dose escalation method will be used for the subsequent dose groups. The entire duration of 28 days after the first dose of ZG006 is defined as the dose-limiting toxicity (DLT).

Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.

Outcomes

Primary Outcome Measures

The incidence of dose-limiting toxicity (DLT)
An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria
Maximum Tolerated Dose (MTD) of ZG006
Determine the Recommended Phase 2 Dose (RP2D)
Number of participants with adverse events (AEs)
The types and frequencies of adverse events (AEs) evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0
Number of participants with serious adverse events (SAEs)
Incidence of abnormal laboratory results
Abnormal laboratory results of safety concerns such as ALT, AST, Cr and BUN, et al according to NCI-CTCAE 5.0 classification.
Changes of ECGs from baselines
Changes of ECGs from baselines, such as QT interval

Secondary Outcome Measures

Objective response rate (ORR)
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Duration of response (DOR)
DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause
disease control rate (DCR)
Maximum plasma concentration (Cmax) of ZG006
Time to peak concentration (Tmax)
AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of ZG006
Terminal phase half-life (t1/2) of ZG006

Full Information

First Posted
July 28, 2023
Last Updated
October 20, 2023
Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05978284
Brief Title
Study of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma
Official Title
A Phase 1/2 Dose Escalation Study of the Tolerability, Safety, Efficacy and Pharmacokinetics of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a multi-center, open-label, Phase Ⅰ/Ⅱ clinical study of ZG006 for the treatment of participants with small cell lung cancer or neuroendocrine carcinoma who had no standard treatment available, or were intolerant to standard treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer, Neuroendocrine Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
During the dose-escalation, an accelerated titration design (ATD) will be utilized for the first two dose groups (0.03mg and 0.1 mg), and the conventional "3+3" dose escalation method will be used for the subsequent dose groups. The entire duration of 28 days after the first dose of ZG006 is defined as the dose-limiting toxicity (DLT).
Arm Title
Part 2: Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.
Intervention Type
Biological
Intervention Name(s)
ZG006
Intervention Description
ZG006 will be administered as an intravenous (IV) infusion.
Primary Outcome Measure Information:
Title
The incidence of dose-limiting toxicity (DLT)
Description
An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the dose-limiting toxicity criteria
Time Frame
Up to 28 days
Title
Maximum Tolerated Dose (MTD) of ZG006
Time Frame
Up to approximately 1 year
Title
Determine the Recommended Phase 2 Dose (RP2D)
Time Frame
Up to approximately 1 year
Title
Number of participants with adverse events (AEs)
Description
The types and frequencies of adverse events (AEs) evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0
Time Frame
Up to approximately 2 year
Title
Number of participants with serious adverse events (SAEs)
Time Frame
Up to approximately 2 year
Title
Incidence of abnormal laboratory results
Description
Abnormal laboratory results of safety concerns such as ALT, AST, Cr and BUN, et al according to NCI-CTCAE 5.0 classification.
Time Frame
Up to approximately 2 year
Title
Changes of ECGs from baselines
Description
Changes of ECGs from baselines, such as QT interval
Time Frame
Up to approximately 2 year
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Time Frame
Up to approximately 2 year
Title
Duration of response (DOR)
Description
DOR is defined as the time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause
Time Frame
Up to approximately 2 year
Title
disease control rate (DCR)
Time Frame
Up to approximately 2 year
Title
Maximum plasma concentration (Cmax) of ZG006
Time Frame
Baseline and up to approximately 1 year
Title
Time to peak concentration (Tmax)
Time Frame
Up to approximately 1 year
Title
AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of ZG006
Time Frame
Up to approximately 1 year
Title
Terminal phase half-life (t1/2) of ZG006
Time Frame
Up to approximately 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fully understand the study and voluntarily sign the informed consent form; Male or female 18~75 years of age; Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), who had no standard treatment available, or were intolerant to standard treatments; Archival tissue sample or fresh biopsy tissue sample must be available for DLL3 detection; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Life expectancy ≥ 3 months; Must have evaluable or measurable lesion. For lesions that have received radiation therapy, only after the progression of the lesions, they can be considered evaluable or measurable lesions; All adverse events from prior treatment have either returned to baseline or CTCAE 5.0 ≤ Grade 1, except for AEs not constituting a safety risk in the opinions of the investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone replacement, etc.; Female and Male patients must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug. Exclusion Criteria: Patients having received any of the following treatments: Anti-DLL3 and anti-CD3 drugs (including investigational drugs); Chemotherapy, biotherapy, endocrine therapy (except for hormone replacement), and biological targeted medicines ≤ 4 weeks before the study entry. Local palliative radiotherapy and a small molecule targeted therapy ≤ 2 weeks (or 5 half-lives, whichever is longer) before the study entry; Systemic immunosuppressive medications, such as corticosteroid (doses > 10 mg/day prednisone or equivalent dose) within 14 days prior to the study entry; Use of any vaccines against viral infections (COVID-19, influenza, varicella, etc.) within 4 weeks of study entry; Received any blood transfusion, EPO, G-CSF, albumin infusion and renal replacement therapy within 14 days prior to study entry. The main organ function meets any of the following criteria within 7 days prior to study entry; Hematological function: ANC < 1.5×10^9/L, PLT < 75×10^9/L, Hemoglobin (Hb) < 100 g/L; Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3×ULN, ALT and AST ≥ 5×ULN for liver metastases patients; Total bilirubin (TBIL) ≥ 1.5×ULN; albumin < 30g/L; Creatinine clearance (Cockcroft-Gault formula) < 50 mL/min; INR > 1.5 or APTT > 1.5×ULN; Medical history, computed tomography (CT) or magnetic resonance imaging (MRI) results indicate the existence of central nervous system (CNS) metastases; Note: Not applicable to the following conditions: subjects with stable CNS metastases; Uncontrollable third cavity effusion (e.g. a large amount of pleural effusion, ascites, or pericardial effusion, etc.) requiring repeated drainage, which was judged by the investigator to be unsuitable for study; Any other malignancy within 5 years (other than radically removed and has not recurred tumors including basal cell skin carcinoma, squamous cell skin carcinoma, superficial bladder cancer, localized prostate cancer, cervical cancer and other cancer in situ, etc.); Severe cardiac-cerebral vascular disease, including but not limited to: Acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or stent implantation within 6 months before study entry; New York Heart Association functional class II to IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50% or the lower limit of normal; Uncontrollable hypertension (even though the best treatment is used but systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg). QTc (F) interval prolonged in electrocardiography during the screening baseline period (> 480 ms) History of autoimmune disease, including but not limited to systemic lupus erythematosus, nephritis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis (except for the following: type I diabetes mellitus, skin diseases that do not require systemic treatment (such as vitiligo), controllable celiac disease, and childhood asthma that completely resolved in adulthood without intervention); Active infection (such as acute bacterial infection, tuberculosis, active hepatitis B/C, active syphilis, or active human immunodeficiency virus infection). Active hepatitis B is defined as: hepatitis B virus DNA titer > 10000 copies/mL or 2000 IU/mL; active hepatitis C is defined as: a positive hepatitis C antibody and HCV viral load above the limit of quantification; active human immunodeficiency virus infection is defined as: antibody positive; Active neurologic paraneoplastic syndrome; Interstitial lung disease or non-infectious pneumonitis (other than radiation-induced pneumonia); Having received prior allogeneic stem cell transplantation or solid organ transplantation; Known allergy to other mAbs or any antibody excipients; the history of a severe allergic reaction, anaphylactoid or other hypersensitivity reactions to humanized antibodies or fusion proteins; Known history of diagnosed neurological or mental disorders, for example, epilepsy, dementia, etc.; A female who is pregnant or nursing; Patients were deemed unsuitable for participating in the study by the investigator for any reason.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hewen Yin
Phone
+86-02158942758
Email
yinhw@zelgen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qiming Wang
Organizational Affiliation
Henan Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
Country
China

12. IPD Sharing Statement

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Study of ZG006 in Participants With Small Cell Lung Cancer or Neuroendocrine Carcinoma

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