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Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures (EMPIRE)

Primary Purpose

Adult Soft Tissue Sarcoma, Non Small Cell Lung Cancer, Triple Negative Breast Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ezabenlimab + BI907828
Sponsored by
Institut Bergonié
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Soft Tissue Sarcoma focused on measuring Tertiary lymphoid structures

Eligibility Criteria

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

Inclusion Criteria: Histologically or cytologically confirmed diagnosis: For cohort A: soft-tissue sarcoma. As recommended by the French NCI, diagnosis must be reviewed or confirmed by the RRePS Network (Réseau de référence en pathologie des sarcomes et des viscères) as recommended by the French NCI (Institut National du Cancer, Inca). For cohort B: non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC) Age ≥ 18 years, Advanced/unresectable and/or metastatic disease, Mature TLS positive status TP53-wild type status known (by molecular biology) Cohort A: MDM2 status known at the time of inclusion Cohort B: are eligible the following populations NSCLC known PD-L1 tumor proportion score (TPS) < 50% AND naïve from treatment with ICI (immune checkpoint inhibitors) NSCLC exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) TNBC exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) MSS-CCR naïve from treatment with ICI Biliary tract cancer exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) Patients must have measurable disease (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as > 10 mm with spiral CT scan., Performance status 0-2 Life expectancy ≥ 8 weeks, Adequate hematologic and end-organ function as defined per protocol Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia and vitiligo of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0), Ability to comply with the study protocol, in the investigator's judgment Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment. Serum or urine pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication, Both women of childbearing potential and men must agree to use two medically acceptable methods of contraception throughout the treatment period No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for: a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year, Voluntarily signed and dated written informed consent prior to any study specific procedure, Patients with a social security in compliance with the French law. Exclusion Criteria: Prior treatment with ezabenlimab and/or BI 907828, Women who are pregnant or breast feeding, Participation to a study involving a medical or therapeutic intervention in the last 30 days, Previous enrolment in the present study, Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons, Inability to swallow, History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins, Known hypersensitivity to Chinese hamster ovary cell products or to any component of the ezabenlimab or BI 907828 formulation, Symptomatic or actively progressing central nervous system (CNS) metastases. History of leptomeningeal disease, Primary CNS tumors with any of the following characteristics: History of intracranial hemorrhage or spinal cord hemorrhage Neurosurgical resection or brain biopsy to the primary brain tumor within 28 days of Cycle 1 Day 1 Any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of ezabenlimab combined with BI 907828, Whole brain radiotherapy within 14 days prior to start of BI 754091 combined with BI 907828 Stereotactic radiosurgery within 7 days prior to start of ezabenlimab combined with BI 907828 Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease) History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study Incomplete recovery from any surgery prior to the start of ezabenlimab combined with BI 907828 that would interfere with the determination of safety or efficacy of ezabenlimab combined with BI 907828 Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina Uncontrolled tumor-related pain. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Active or history of autoimmune disease or immune deficiency, History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. Active tuberculosis Severe infection within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of ezabenlimab combined with BI 907828. Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for such a vaccine during treatment or within 6 months after the final dose ezabenlimab combined with BI 907828. Seasonal flu vaccines that do not contain a live virus are permitted, Current treatment with anti-viral therapy for HBV Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of ezabenlimab combined with BI 907828 Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for systemic immunosuppressive medication during ezabenlimab combined with BI 907828. Patients with oral anticoagulation based on Vitamin K antagonist.

Sites / Locations

  • Institut Bergonié
  • Centre Georges François Leclerc
  • Centre Oscar Lambret
  • Centre Léon Bérard
  • CHRU Poitiers
  • Centre Eugène Marquis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort A: soft-tissue sarcomas

Cohort B: Solid tumors

Arm Description

Soft-tissue sarcomas

Solid tumors [non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC)]

Outcomes

Primary Outcome Measures

Disease control rate (DCR)
Disease control rate (DCR), defined as the proportion of patients with disease control lasting for at least 24 weeks since treatment onset, will be reported.

Secondary Outcome Measures

Objective response rate
Objective response rate (ORR), defined as the proportion of patients with objective response will be assessed, based on centralized radiological review, within 24 weeks of treatment onset.
Duration of response (DoR)
Duration of response (DoR) defined as the time from documentation of tumor response (CR, Cru, PR, PRu) to disease progression (as per RECIST V1.1).
Progression-free survival (PFS)
Progression-free survival (PFS) defined as the time from the first day of treatment to the first documented disease progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first.
Overall survival
Overall survival defined as the time from the first day of treatment to death (due to any cause).
Safety and tolerability of the combination
Occurence of adverse events (AEs) and Serious adverse events (SAEs)

Full Information

First Posted
October 10, 2023
Last Updated
October 19, 2023
Sponsor
Institut Bergonié
Collaborators
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT06084689
Brief Title
Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures
Acronym
EMPIRE
Official Title
Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
July 1, 2026 (Anticipated)
Study Completion Date
January 1, 2027 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
Phase II, multicenter, open-label, multi-cohort proof-of-concept study designed to evaluate the safety and efficacy of Ezabenlimab combined with BI 907828 in patients with unresectable, locally advanced or metastatic solid tumors.
Detailed Description
This study is a phase II, multicenter, open-label, multi-cohort proof-of-concept study designed to evaluate the safety and efficacy of Ezabenlimab combined with BI 907828 in patients with unresectable, locally advanced or metastatic solid tumors. Inclusions will proceed independently for 2 cohorts of patients with TP53 wild-type and TLS+ tumors (TLS: tertiary lymphoid strucutres), as follows: Cohort A: soft-tissue sarcomas Single-arm phase II trial 2-stage optimal Simon's design (Simon, 1989) Primary endpoint: is Disease Control Rate (DCR) within 24 weeks of treatment onset, as per RECIST v1.1. Cohort B: Solid tumors [non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC)] Single-arm phase II trial 2-stage optimal Simon's design (Simon, 1989) Primary endpoint: is Disease Control Rate (DCR) within 24 weeks of treatment onset, as per RECIST v1.1.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Soft Tissue Sarcoma, Non Small Cell Lung Cancer, Triple Negative Breast Cancer, Colorectal Cancer, Biliary Tract Cancer
Keywords
Tertiary lymphoid structures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
2 single-arm phase II trials: Cohort A: soft-tissue sarcomas Cohort B: Solid tumors [non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC)]
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: soft-tissue sarcomas
Arm Type
Experimental
Arm Description
Soft-tissue sarcomas
Arm Title
Cohort B: Solid tumors
Arm Type
Experimental
Arm Description
Solid tumors [non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC)]
Intervention Type
Drug
Intervention Name(s)
Ezabenlimab + BI907828
Intervention Description
A treatment cycle consists of 3 weeks. Both treatments will be administered on Day 1 of each cycle.
Primary Outcome Measure Information:
Title
Disease control rate (DCR)
Description
Disease control rate (DCR), defined as the proportion of patients with disease control lasting for at least 24 weeks since treatment onset, will be reported.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Objective response rate (ORR), defined as the proportion of patients with objective response will be assessed, based on centralized radiological review, within 24 weeks of treatment onset.
Time Frame
6 months
Title
Duration of response (DoR)
Description
Duration of response (DoR) defined as the time from documentation of tumor response (CR, Cru, PR, PRu) to disease progression (as per RECIST V1.1).
Time Frame
1 year
Title
Progression-free survival (PFS)
Description
Progression-free survival (PFS) defined as the time from the first day of treatment to the first documented disease progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first.
Time Frame
1 year
Title
Overall survival
Description
Overall survival defined as the time from the first day of treatment to death (due to any cause).
Time Frame
1 year
Title
Safety and tolerability of the combination
Description
Occurence of adverse events (AEs) and Serious adverse events (SAEs)
Time Frame
Throughout treatment period, an expected average of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed diagnosis: For cohort A: soft-tissue sarcoma. As recommended by the French NCI, diagnosis must be reviewed or confirmed by the RRePS Network (Réseau de référence en pathologie des sarcomes et des viscères) as recommended by the French NCI (Institut National du Cancer, Inca). For cohort B: non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC) Age ≥ 18 years, Advanced/unresectable and/or metastatic disease, Mature TLS positive status TP53-wild type status known (by molecular biology) Cohort A: MDM2 status known at the time of inclusion Cohort B: are eligible the following populations NSCLC known PD-L1 tumor proportion score (TPS) < 50% AND naïve from treatment with ICI (immune checkpoint inhibitors) NSCLC exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) TNBC exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) MSS-CCR naïve from treatment with ICI Biliary tract cancer exposed to anti-PD1 or PD-L1 based therapy with clinical benefit (clinical benefit is defined as objective response or stable disease for at least 4 months) Patients must have measurable disease (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as > 10 mm with spiral CT scan., Performance status 0-2 Life expectancy ≥ 8 weeks, Adequate hematologic and end-organ function as defined per protocol Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia and vitiligo of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0), Ability to comply with the study protocol, in the investigator's judgment Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment. Serum or urine pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication, Both women of childbearing potential and men must agree to use two medically acceptable methods of contraception throughout the treatment period No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for: a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year, Voluntarily signed and dated written informed consent prior to any study specific procedure, Patients with a social security in compliance with the French law. Exclusion Criteria: Prior treatment with ezabenlimab and/or BI 907828, Women who are pregnant or breast feeding, Participation to a study involving a medical or therapeutic intervention in the last 30 days, Previous enrolment in the present study, Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons, Inability to swallow, History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins, Known hypersensitivity to Chinese hamster ovary cell products or to any component of the ezabenlimab or BI 907828 formulation, Symptomatic or actively progressing central nervous system (CNS) metastases. History of leptomeningeal disease, Primary CNS tumors with any of the following characteristics: History of intracranial hemorrhage or spinal cord hemorrhage Neurosurgical resection or brain biopsy to the primary brain tumor within 28 days of Cycle 1 Day 1 Any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of ezabenlimab combined with BI 907828, Whole brain radiotherapy within 14 days prior to start of BI 754091 combined with BI 907828 Stereotactic radiosurgery within 7 days prior to start of ezabenlimab combined with BI 907828 Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease) History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study Incomplete recovery from any surgery prior to the start of ezabenlimab combined with BI 907828 that would interfere with the determination of safety or efficacy of ezabenlimab combined with BI 907828 Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina Uncontrolled tumor-related pain. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Active or history of autoimmune disease or immune deficiency, History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. Active tuberculosis Severe infection within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of ezabenlimab combined with BI 907828. Prior allogeneic stem cell or solid organ transplantation Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for such a vaccine during treatment or within 6 months after the final dose ezabenlimab combined with BI 907828. Seasonal flu vaccines that do not contain a live virus are permitted, Current treatment with anti-viral therapy for HBV Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of ezabenlimab combined with BI 907828 Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for systemic immunosuppressive medication during ezabenlimab combined with BI 907828. Patients with oral anticoagulation based on Vitamin K antagonist.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antoine ITALIANO, MD, PhD
Phone
+33556333333
Email
a.italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Simone MATHOULIN PELISSIER, MD, PhD
Email
s.mathoulin@bordeaux.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO, MD, PhD
Organizational Affiliation
Institut Bergonié
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine Italiano, MD, PhD
Facility Name
Centre Georges François Leclerc
City
Dijon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François Ghiringhelli, MD, PhD
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Loïc Lebellec, MD
Facility Name
Centre Léon Bérard
City
Lyon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Armelle Dufresne, MD
Facility Name
CHRU Poitiers
City
Poitiers
Country
France
Facility Name
Centre Eugène Marquis
City
Rennes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xavier Choderlos de Laclos, MD

12. IPD Sharing Statement

Learn more about this trial

Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures

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