Trial Title:
Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures
NCT ID:
NCT06084689
Condition:
Adult Soft Tissue Sarcoma
Non Small Cell Lung Cancer
Triple Negative Breast Cancer
Colorectal Cancer
Biliary Tract Cancer
Conditions: Official terms:
Sarcoma
Triple Negative Breast Neoplasms
Biliary Tract Neoplasms
Tertiary Lymphoid Structures
Conditions: Keywords:
Tertiary lymphoid structures
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention 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)]
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ezabenlimab + BI907828
Description:
A treatment cycle consists of 3 weeks. Both treatments will be administered on Day 1 of
each cycle.
Arm group label:
Cohort A: soft-tissue sarcomas
Arm group label:
Cohort B: Solid tumors
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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)
2. Age ≥ 18 years,
3. Advanced/unresectable and/or metastatic disease,
4. Mature TLS positive status
5. TP53-wild type status known (by molecular biology)
6. Cohort A: MDM2 status known at the time of inclusion
7. 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)
8. 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.,
9. Performance status 0-2
10. Life expectancy ≥ 8 weeks,
11. Adequate hematologic and end-organ function as defined per protocol
12. Disease progression on prior treatment, or previously untreated disease with no
available acceptable treatment
13. 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),
14. Ability to comply with the study protocol, in the investigator's judgment
15. 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,
16. Both women of childbearing potential and men must agree to use two medically
acceptable methods of contraception throughout the treatment period
17. 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,
18. Voluntarily signed and dated written informed consent prior to any study specific
procedure,
19. Patients with a social security in compliance with the French law.
Exclusion Criteria:
1. Prior treatment with ezabenlimab and/or BI 907828,
2. Women who are pregnant or breast feeding,
3. Participation to a study involving a medical or therapeutic intervention in the last
30 days,
4. Previous enrolment in the present study,
5. Patient unable to follow and comply with the study procedures because of any
geographical, social or psychological reasons,
6. Inability to swallow,
7. History of severe allergic anaphylactic reactions to chimeric or humanized
antibodies or fusion proteins,
8. Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the ezabenlimab or BI 907828 formulation,
9. Symptomatic or actively progressing central nervous system (CNS) metastases.
10. History of leptomeningeal disease,
11. 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
12. Any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is
shorter) prior to start of ezabenlimab combined with BI 907828,
13. Whole brain radiotherapy within 14 days prior to start of BI 754091 combined with BI
907828
14. Stereotactic radiosurgery within 7 days prior to start of ezabenlimab combined with
BI 907828
15. 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)
16. 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
17. 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
18. 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
19. Uncontrolled tumor-related pain.
20. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently).
21. Active or history of autoimmune disease or immune deficiency,
22. 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.
23. Active tuberculosis
24. 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
25. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of ezabenlimab combined with BI 907828.
26. Prior allogeneic stem cell or solid organ transplantation
27. 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,
28. Current treatment with anti-viral therapy for HBV
29. 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
30. 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.
31. Patients with oral anticoagulation based on Vitamin K antagonist.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Bergonié
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Contact:
Last name:
Antoine Italiano, MD, PhD
Facility:
Name:
Centre Georges François Leclerc
Address:
City:
Dijon
Country:
France
Contact:
Last name:
François Ghiringhelli, MD, PhD
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Zip:
59000
Country:
France
Contact:
Last name:
Loïc Lebellec, MD
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Country:
France
Contact:
Last name:
Armelle Dufresne, MD
Facility:
Name:
CHRU Poitiers
Address:
City:
Poitiers
Country:
France
Facility:
Name:
Centre Eugène Marquis
Address:
City:
Rennes
Country:
France
Contact:
Last name:
Xavier Choderlos de Laclos, MD
Start date:
January 1, 2024
Completion date:
January 1, 2027
Lead sponsor:
Agency:
Institut Bergonié
Agency class:
Other
Collaborator:
Agency:
Boehringer Ingelheim
Agency class:
Industry
Source:
Institut Bergonié
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06084689
