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A Study to Test How Well Different Doses of BI 764532 in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3

Primary Purpose

Small Cell Lung Carcinoma (SCLC), Neuroendocrine Neoplasms

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BI 764532
Ezabenlimab
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma (SCLC)

Eligibility Criteria

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

Inclusion criteria Age ≥18 years Signed and dated, written informed consent form (main ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses. Diagnosed with locally advanced, metastatic or relapsed cancer not amenable to curative treatment of the following histologies: Small cell lung carcinoma (SCLC) Large cells neuroendocrine lung carcinoma(LCNEC) Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin Tumours must be positive for Delta-like 3 (DLL3) expression (on archived tissue) according to central pathology review in order to start BI 764532 . Patients with tumors with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumor tissue. Patient who failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted available treatment options known to prolong survival for their disease. Previous therapies should include at least one line of platinum-based chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. At least one evaluable lesion outside of Central Nervous System (CNS) as defined per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Subjects with brain metastases are eligible provided they meet the following criteria: radiotherapy or surgery for brain metastases was completed at least 2 weeks or 4 weeks respectively, prior to the first administration of BI 764532 patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant CNS disease. Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.These methods must be used during the study and for at least 3 months after the last dose of BI 764532. A list of contraception methods meeting these criteria is provided in the patient information. Further inclusion criteria apply. Exclusion criteria Previous treatment with T-cell-engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like RovaT) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy. Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except: effectively treated non-melanoma skin cancers effectively treated carcinoma in situ of the cervix effectively treated ductal carcinoma in situ other effectively treated malignancy that is considered cured by local treatment Major injuries and/or surgery or bone fracture within 28 days of first dose BI 764532, or planned surgical procedures Known leptomeningeal disease or spinal cord compression due to metastatic disease Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed Active infection that requires medical therapy or other clinically significant intervention Severe acute respiratory syndrome coronavirus 2 (SARS COV2) infection within 2 weeks prior to study entry (confirmed via Polymerase chain reaction (PCR) test or other applicable test as per local requirements) or suspected SARS-CoV-2 infection as per physician assessment, or close contact (within 1 week) with an individual with confirmed SARS-CoV-2 infection Any of the following known laboratory evidence of hepatitis virus infection: Positive results of hepatitis B surface (HBs) antigen Presence of hepatitis B core (HBc) antibody together with hepatitis B virus (HBV)-Deoxyribonucleic Acid (DNA) Presence of hepatitis C Ribonucleic acid (RNA) Further exclusion criteria apply.

Sites / Locations

  • Brussels - UNIV Saint-LucRecruiting
  • UNIV UZ GentRecruiting
  • Universitätsklinikum Carl Gustav Carus DresdenRecruiting
  • National Cancer Center HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BI 764532 + ezabenlimab treatment group

Arm Description

Successive cohorts of patients will receive increasing doses of BI 764532 in combination with ezabenlimab until the maximum tolerated dose (MTD) is reached, or upon decision of Dose Escalation Committee (DEC).

Outcomes

Primary Outcome Measures

Occurrence of Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) evaluation period

Secondary Outcome Measures

Occurrence of DLTs during the on-treatment period
Objective response, defined as best overall response of complete response (CR) or partial response (PR)
Objective response, defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined by the investigator's assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in patients with measurable disease from date of first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent
Cmax (maximum measured concentration of BI 764532)
Cmax (maximum measured concentration of ezabenlimab)
AUCτ (area under the concentration-time curve of BI 764532 over a uniform dosing interval τ)
AUCτ (area under the concentration-time curve of ezabenlimab) over a uniform dosing interval τ)

Full Information

First Posted
May 25, 2023
Last Updated
October 17, 2023
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT05879978
Brief Title
A Study to Test How Well Different Doses of BI 764532 in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3
Official Title
A Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 764532 Combined With Ezabenlimab in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2023 (Actual)
Primary Completion Date
October 30, 2024 (Anticipated)
Study Completion Date
October 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

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

5. Study Description

Brief Summary
This study is open to adults with small cell lung cancer and other neuroendocrine tumours that are positive for the tumour marker Delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find out the highest dose of BI 764532 that people can tolerate when taken together with another medicine called ezabenlimab. BI 764532 and ezabenlimab are antibodies that may help the immune system fight cancer. Participants get BI 764532 and ezabenlimab as infusions into a vein. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about every week. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma (SCLC), Neuroendocrine Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BI 764532 + ezabenlimab treatment group
Arm Type
Experimental
Arm Description
Successive cohorts of patients will receive increasing doses of BI 764532 in combination with ezabenlimab until the maximum tolerated dose (MTD) is reached, or upon decision of Dose Escalation Committee (DEC).
Intervention Type
Drug
Intervention Name(s)
BI 764532
Intervention Description
BI 764532
Intervention Type
Drug
Intervention Name(s)
Ezabenlimab
Intervention Description
Ezabenlimab
Primary Outcome Measure Information:
Title
Occurrence of Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) evaluation period
Time Frame
up to 17 months
Secondary Outcome Measure Information:
Title
Occurrence of DLTs during the on-treatment period
Time Frame
up to 17 months
Title
Objective response, defined as best overall response of complete response (CR) or partial response (PR)
Description
Objective response, defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined by the investigator's assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in patients with measurable disease from date of first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent
Time Frame
up to 17 months
Title
Cmax (maximum measured concentration of BI 764532)
Time Frame
up to 17 months
Title
Cmax (maximum measured concentration of ezabenlimab)
Time Frame
up to 17 months
Title
AUCτ (area under the concentration-time curve of BI 764532 over a uniform dosing interval τ)
Time Frame
up to 17 months
Title
AUCτ (area under the concentration-time curve of ezabenlimab) over a uniform dosing interval τ)
Time Frame
up to 17 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Age ≥18 years Signed and dated, written informed consent form (main ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses. Diagnosed with locally advanced, metastatic or relapsed cancer not amenable to curative treatment of the following histologies: Small cell lung carcinoma (SCLC) Large cells neuroendocrine lung carcinoma(LCNEC) Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin Tumours must be positive for Delta-like 3 (DLL3) expression (on archived tissue) according to central pathology review in order to start BI 764532 . Patients with tumors with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumor tissue. Patient who failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted available treatment options known to prolong survival for their disease. Previous therapies should include at least one line of platinum-based chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. At least one evaluable lesion outside of Central Nervous System (CNS) as defined per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Subjects with brain metastases are eligible provided they meet the following criteria: radiotherapy or surgery for brain metastases was completed at least 2 weeks or 4 weeks respectively, prior to the first administration of BI 764532 patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant CNS disease. Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.These methods must be used during the study and for at least 3 months after the last dose of BI 764532. A list of contraception methods meeting these criteria is provided in the patient information. Further inclusion criteria apply. Exclusion criteria Previous treatment with T-cell-engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like RovaT) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy. Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except: effectively treated non-melanoma skin cancers effectively treated carcinoma in situ of the cervix effectively treated ductal carcinoma in situ other effectively treated malignancy that is considered cured by local treatment Major injuries and/or surgery or bone fracture within 28 days of first dose BI 764532, or planned surgical procedures Known leptomeningeal disease or spinal cord compression due to metastatic disease Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed Active infection that requires medical therapy or other clinically significant intervention Severe acute respiratory syndrome coronavirus 2 (SARS COV2) infection within 2 weeks prior to study entry (confirmed via Polymerase chain reaction (PCR) test or other applicable test as per local requirements) or suspected SARS-CoV-2 infection as per physician assessment, or close contact (within 1 week) with an individual with confirmed SARS-CoV-2 infection Any of the following known laboratory evidence of hepatitis virus infection: Positive results of hepatitis B surface (HBs) antigen Presence of hepatitis B core (HBc) antibody together with hepatitis B virus (HBV)-Deoxyribonucleic Acid (DNA) Presence of hepatitis C Ribonucleic acid (RNA) Further exclusion criteria apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boehringer Ingelheim
Phone
1-800-243-0127
Email
clintriage.rdg@boehringer-ingelheim.com
Facility Information:
Facility Name
Brussels - UNIV Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Phone
080049616
Email
belgique@bitrialsupport.com
Facility Name
UNIV UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Phone
080049616
Email
belgique@bitrialsupport.com
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Phone
08007234742
Email
deutschland@bitrialsupport.com
Facility Name
National Cancer Center Hospital
City
Tokyo, Chuo-ku
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Phone
0120201230
Email
nippon@bitrialsupport.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
IPD Sharing Time Frame
After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
IPD Sharing Access Criteria
For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
IPD Sharing URL
https://www.mystudywindow.com/msw/datasharing
Links:
URL
https://www.mystudywindow.com
Description
Related Info

Learn more about this trial

A Study to Test How Well Different Doses of BI 764532 in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3

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