Ended Therapeutic exploratory (Phase II) Adult patients with locally advanced/metastatic solid tumors

EMPIRE : Targeting MDM2 and PD1 in tumors with tertiary lymphoid structures

EU CTIS ID: 2023-506823-28-00

What this study is testing

To investigate the antitumor activity of ezabenlimab combined with BI 907828 independently for 2 cohorts of participants : - [Cohort A] Participants with soft-tissue sarcoma, - [Cohort B] Participants with 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)] In both cohorts, antitumor activity will be assessed in terms of disease control, as per RECIST v1.1.

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

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)
Life expectancy ≥ 8 weeks
Adequate hematologic and end-organ function as defined below: a) Abolute neutrophil count (ANC) ≥ 1.5 G/l b) Platelet count ≥ 100 G/l c) Hemoglobin ≥ 8.5 g/dL (if applicable, previous transfusion at least 4 weeks before screening laboratory assessment) d) Total bilirubin ≤ 1.5 x upper limit of normal (ULN), with the following exception: patients with known Gilbert’s syndrome who have a serum bilirubin ≤ 3 x ULN may be enrolled. e) AST and ALT ≤ 2.5 x ULN, with the following exception: patients with liver metastases who have an AST or ALT ≤ 5 x ULN may be enrolled. f) Uncontrolled or symptomatic hypercalcemia (ionized calcium ≤ 1.5 mmol/L, calcium ≤ 12 mg/dL, or corrected calcium ≤ ULN) g) INR or PT and aPTT ≤ 1.5 x ULN
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

You likely can't join if

Prior treatment with ezabenlimab and/or BI 907828,
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of ezabenlimab combined with BI 907828. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
Prior allogeneic stem cell or solid organ transplantation
History of leptomeningeal disease
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

See the full eligibility criteria

Who can join

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)
Life expectancy ≥ 8 weeks
Adequate hematologic and end-organ function as defined below: a) Abolute neutrophil count (ANC) ≥ 1.5 G/l b) Platelet count ≥ 100 G/l c) Hemoglobin ≥ 8.5 g/dL (if applicable, previous transfusion at least 4 weeks before screening laboratory assessment) d) Total bilirubin ≤ 1.5 x upper limit of normal (ULN), with the following exception: patients with known Gilbert’s syndrome who have a serum bilirubin ≤ 3 x ULN may be enrolled. e) AST and ALT ≤ 2.5 x ULN, with the following exception: patients with liver metastases who have an AST or ALT ≤ 5 x ULN may be enrolled. f) Uncontrolled or symptomatic hypercalcemia (ionized calcium ≤ 1.5 mmol/L, calcium ≤ 12 mg/dL, or corrected calcium ≤ ULN) g) INR or PT and aPTT ≤ 1.5 x ULN
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 and for: - Women: 6 months and 12 days after end of BI 907828; 6 months after end of ezabenlimab. - Men: 102 days after end of BI 907828; 11 months after end of ezabenlimab
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
Age ≥ 18 years
Advanced/unresectable and/or metastatic disease
Mature TLS positive status: tumors will be considered mature TLS-positive when containing either a visible germinal center on HES or a meshwork of CD23+ follicular dendritic cells or isolated CD23+ dendritic cell if the cell harbored a morphology fitting with dendritic differentiation (i.e., cytoplasmic dendritic extensions). Mature TLS displaying germinal centers visible on HES are confirmed with a double CD20/CD23 staining. Note that for TLS status, ensure the availability of archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample or tumor material newly obtained by biopsy. Except if TLS analysis have been already performed by Biopathological platform at Bergonié Institute, presence or absence of TLS should be confirmed by central
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 AND for whom standard treatments are not indicated or have been deemed unsuitable based on their clinical condition and in consultation with their treating physicians - 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). - Patients with the following targetable genomic alterations must have received the corresponding targeted therapy or be excluded unless contraindications to these therapies exist or treatment is not available/reimbursed in the site country: • EGFR Exon 19 Deletion or Exon 21 L858R • EGFR Exon 20 Insertion Mutation • ALK Rearrangement • KRAS G12C Mutation • ROS1 Rearrangement • BRAF V600E Mutation • MET Exon 14 Skipping Mutation • RET Rearrangement 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) - For patients with genetically confirmed BRCA1/2 mutations (gBRCAm): patients who previously received treatment with a PARP inhibitor, except if they presented contraindications to such treatment. - For all patients, including those with HER2-low expressed tumors: patients who previously received treatment with sacituzumab govitecan or trastuzumab deruxtecan, except if they were considered ineligible to this treatment due to medical reasons. MSS-CCR naïve from treatment with ICI - Patients must have received the following treatments: fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF, anti-EGFR if RASwt and anti-BRAF if BRAF mutated, except if they presented contraindications to such treatments. - - For patients with liver metastases only, these metastases have to be unresectable. BTC - 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). - For patients diagnosed with intrahepatic cholangiocarcinoma harboring FGFR mutations (FGFRm) or IDH mutations (IDHm): these patients must have received the corresponding targeted therapy, in accordance with current treatment guidelines and best practices, unless contraindications to these therapies exist.
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

What rules you out

Prior treatment with ezabenlimab and/or BI 907828,
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of ezabenlimab combined with BI 907828. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
Prior allogeneic stem cell or solid organ transplantation
History of leptomeningeal disease
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 (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of ezabenlimab combined with BI 907828
Participation to a study involving a medical or therapeutic intervention in the last 30 days,
Treatment with systemic immunosuppressive medication (including, but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for systemic immunosuppressive medication during ezabenlimabcombined with BI 907828, with the following exceptions: - Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy, a one-time dose of dexamethasone for nausea or chronic use of ≤10 mg/day of prednisone or dose-equivalent corticosteroid) are eligible for the study. The use of inhaled corticosteroids is allowed. - Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
Patients with oral anticoagulation based on Vitamin K antagonist.
Previous enrolment in the present study,
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
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,
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
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the ezabenlimabor BI 907828 formulation,
Symptomatic or actively progressing central nervous system (CNS) metastases. Note that asymptomatic patients with treated or untreated CNS metastases are eligible, provided that all of the following criteria are met: - No ongoing requirement for corticosteroids as therapy for CNS metastases - No evidence of interim progression between completion of CNS-directed therapy and screening radiographic study - No history of intracranial hemorrhage or spinal cord hemorrhage
Prohibited concomitant medication specified in section 7.5.2 and 7.5.3 within 3 weeks or 5 half-lives (whichever is shorter) prior to initiation of BI 907828 (during the pre-treatment and treatment phase (including retreatment for post-complete response relapse) of this trial) included CYP2C8 substrates, UGT1A1 substrates, CYP2B6 substrates, narrow therapeutic index drugs that are P-gp and BCRP substrates (digoxin), OATP1B1/B3 inhibitors, strong inhibitors or inducers of CYP3A4.
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
Sterotactic radiosurgery within 7 days prior to start of ezabenlimabcombined with BI 907828
Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
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
33. Participants with a prior history of myeloid malignancies, including myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML)
Women who are pregnant or breast feeding,
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: - Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. - Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. - Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: o rash must cover ≤ 10% of body surface area. o Disease is well controlled at baseline and requires only low-potency topical corticosteroids o No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
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

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.