Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Trial of BI 765063 Monotherapy and in Combination With BI 754091 in Patients With Advanced Solid Tumours

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03990233
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : June 28, 2019
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
OSE Immunotherapeutics

Brief Summary:
This trial will be a two steps Phase I clinical study in patients with advanced solid tumors with an escalating phase (Step 1) followed by an expansion phase (Step 2) of BI 765063, a monoclonal antibody (mAb) antagonist to signal regulatory protein alpha (SIRPα) receptor, a myeloid checkpoint inhibitor administered as single agent, and in combination with BI 754091, a mAb antagonist to PD-1 receptor, a lymphocyte T checkpoint inhibitor.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: BI 765063 Drug: BI 754091 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
  • Step 1 (Dose escalation [Cohorts A and B]) primary objective : In V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumors, Dose-Limiting Toxicities (DLTs), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of BI 765063, as monotherapy (Cohort A) and in combination with BI 754091 (Cohort B).
  • Step 2 (Expansion Cohorts [Cohorts C]) primary objective : In V1/V1 homozygous patients with selected advanced solid tumors, DLT-like events and RP2D confirmation of BI 765063 as monotherapy (Cohort C1) and in combination with BI 754091 (Cohort C2) .
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase I Dose Finding Study of BI 765063, a Monoclonal Antibody (mAb) Antagonist of SIRPα, as Single Agent and in Combination With BI 754091, a Programmed Death-1 (PD-1) mAb, to Characterize Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy in Patients With Advanced Solid Tumours
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Arm Intervention/treatment
Experimental: Step 1 (Dose escalation) : Cohorts A
BI 765063 (SIRPα inhibitor) alone in V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumours
Drug: BI 765063
mAb antagonist to SIRPα receptor, a myeloid checkpoint inhibitor
Other Name: OSE-172

Experimental: Step 1 (Dose escalation) : Cohorts B
BI 765063 (SIRPα inhibitor) in combination with BI 754091 (PD-1 inhibitor) in V1/V1 homozygous and V1/V2 heterozygous patients with advanced solid tumours
Drug: BI 765063
mAb antagonist to SIRPα receptor, a myeloid checkpoint inhibitor
Other Name: OSE-172

Drug: BI 754091
mAb antagonist to PD-1 receptor, a lymphocyte T checkpoint inhibitor

Experimental: Step 2 (Expansion Cohorts) : Cohort C1
BI 765063 (SIRPα inhibitor) alone in V1/V1 homozygous patients with selected advanced solid tumours (e.g. Non-small Cell Lung Carcinoma, Triple Negative Breast cancer, Pancreatic cancer, Melanoma, Head and Neck Squamous Cell Carcinoma, Renal cell carcinoma, Urothelial Carcinoma, Small Cell Lung Cancer, Gastric cancer, Colorectal Cancer and Ovarian cancer)
Drug: BI 765063
mAb antagonist to SIRPα receptor, a myeloid checkpoint inhibitor
Other Name: OSE-172

Experimental: Step 2 (Expansion Cohorts) : Cohort C2
BI 765063 (SIRPα inhibitor) in combination with BI 754091 (PD-1 inhibitor) in V1/V1 homozygous patients with selected advanced solid tumours (e.g. Non-small Cell Lung Carcinoma, Triple Negative Breast cancer, Pancreatic cancer, Melanoma, Head and Neck Squamous Cell Carcinoma, Renal cell carcinoma, Urothelial Carcinoma, Small Cell Lung Cancer, Gastric cancer, Colorectal Cancer and Ovarian cancer)
Drug: BI 765063
mAb antagonist to SIRPα receptor, a myeloid checkpoint inhibitor
Other Name: OSE-172

Drug: BI 754091
mAb antagonist to PD-1 receptor, a lymphocyte T checkpoint inhibitor




Primary Outcome Measures :
  1. Step 1 (dose escalation Parts A and B): Number of patients with Dose-Limiting Toxicities (DLTs) during the first treatment cycle [ Time Frame: 3 weeks (1 cycle) ]
  2. Step 1 (dose escalation Parts A and B): Maximum Tolerated Dose (MTD) determination [ Time Frame: 3 weeks (1 cycle) ]
  3. Step 2 (expansion monotherapy and combination Part C): Number of patients with DLT-like events during the whole treatment [ Time Frame: An average of 1 year ]

Secondary Outcome Measures :
  1. Step 1: Number of patients with DLT-like events during the whole treatment [ Time Frame: An average of 1 year ]
  2. Step 1 and 2: Incidence and severity of all Adverse Events (AEs), Serious AEs (SAEs), AEs of special interest (AESIs), Immune related AEs (irAEs) [ Time Frame: An average of 1 year ]
  3. Step 2: Objective Response Rate (ORR) defined as best response of Complete Response (CR) and Partial Response (PR) as per RECIST v 1.1 criteria [ Time Frame: An average of 1 year ]
  4. Step 1 and 2: Cmax determination [ Time Frame: 12 weeks (4 cycles) ]
  5. Step 1 and 2: AUC 0-tz determination [ Time Frame: Up to 12 weeks (4 cycles) ]
  6. Step 1 and 2: Percentage and evolution of SIRPα receptor occupancy (RO) in blood at pre, on-treatment and after the end of treatment [ Time Frame: Up to 12 weeks (4 cycles) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated, written informed consent form (ICF) prior to any trial-specific procedures.
  2. Male or female aged ≥ 18 years (no upper limit of age) at the time of ICF signature.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Life expectancy of at least 3 months.
  5. Patients with a SIRPα polymorphism including at least one V1 allele will be selected (i.e., homozygous V1/V1 or heterozygous V1/V2 in separate cohorts in escalation [Step 1] and only homozygous V1/V1 in expansion cohorts [Step 2]); SIRPα polymorphism will be assessed in blood sampling (patient DNA) in a central laboratory; V1 allele is understood to include V1 and V1-like alleles.
  6. In Step 1: Patients with histologically or cytologically documented advanced/metastatic primary or recurrent malignancies who failed or are not eligible to standard therapy;

    In Step 2: Patients with histologically or cytologically documented advanced/metastatic primary or recurrent solid tumors who failed or are not eligible to standard therapy with the following tumour types: NSCLC, TNBC, pancreatic cancer, melanoma, HNSCC, RCC, UC, SCL, gastric cancer, CRC and ovarian cancer. Patients included in Step 2 must have no alternative treatment and have been previously treated with the standard of care therapy including chemotherapy, targeted therapy and/or immune check-point inhibitors, as per local guidelines (except if contra-indication and/or ineligibility).

  7. Patients with at least one measurable lesion as per RECIST v1.1.
  8. Patients must agree to pre- and on-treatment tumor biopsies. Fresh tumor biopsy may come either from the primary tumor or from a metastasis. Cytological material is not accepted. Archival tumor biopsy is acceptable, if done within 4 weeks before the first treatment administration.

    Biopsy sites should be carefully selected by the investigator so that it is safe for the patient and subsequent biopsy can be performed at the same location; also if possible should be distinct from the measurable lesion;

  9. Adequate biological parameters defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
    2. Hemoglobin (Hb) level ≥ 10 g/dL. (without recent red blood cell transfusion within 2 weeks prior to study entry)
    3. Platelet count ≥ 100 x 10^9/L.
    4. Total bilirubin level ≤ 1.5 X Upper Limit Normal (ULN), except for patients with Gilbert's syndrome from whom total bilirubin < 3.0 x ULN or direct bilirubin < 1.5 x ULN is authorized.
    5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
    6. Serum creatinine ≤ 1.5 ULN; or creatinine clearance > 50 mL/min (Chronic Kidney Disease Epidemiology [CKD-EPI] formula).
    7. INR ≤ 1.5 (except if patient treated with anti-vitamin K); anticoagulation with anti-vitamin K and Low Molecular Weight Heparin [LMWH] is allowed;
  10. Prior major treatment-related surgery completed at least 28 days before study drug administration;
  11. In all cohorts :

    • An interval of at least 28 days since the last chemotherapy, approved immunotherapy, biological or investigational therapy, radiation or tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib) must have elapsed before the first study drug administration(s);
    • And all toxicities related to previous anticancer therapies have resolved to normal value or ≤ to Grade 1 prior to the study treatment administration, except alopecia.
  12. Women must not be breastfeeding;
  13. Women of childbearing potential (WOCB) must agree to use highly effective methods of contraception (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly), prior to study entry, during the study and for 5 months after the last dose of study drug.

    Highly effective methods of contraception are defined as one of the following methods: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence.

  14. Male patient with WOCBP partner must be willing to use male contraception (condoms) during the study and until 5 months after last dose of study drug. WOCBP partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug (i.e.; oral hormonal contraception, cap, diaphragm, or sponge with spermicide).
  15. Females of childbearing potential must have a serum negative pregnancy test within 7 days prior to first administration. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test.
  16. Capable of understanding and complying with protocol requirements.
  17. Patients must be affiliated to a social security system or an equivalent system.

Exclusion Criteria:

  1. Patient with symptomatic/active central nervous system (CNS) metastases; Patient with previously treated brain metastases are eligible, if there is no evidence of progression for at least 28 days before the first study treatment administration, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period;
  2. Other tumor location necessitating an urgent therapeutic intervention (e.g., palliative care, surgery or radiation therapy, such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture).
  3. Presence of other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.

    Except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment;

  4. Patient with active autoimmune disease or a documented history of autoimmune disease, that requires systemic treatment (i.e. corticosteroids or immunosuppressive drugs).

    Except patients with vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition that does not require systemic therapy, patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and/or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.

  5. Known severe infusion related reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v5.0) and patients removed from previous anti-PD-1 or anti-PD-L1 therapy because of a severe or life-threatening immune-related adverse event (irAE) (Grade ≥ 3 NCI-CTCAE v5.0);
  6. Patients receiving systemic treatment with any immunosuppressive medication within one-week prior treatment start; Steroids of max. 10 mg prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive.
  7. Patients with interstitial lung disease or active, non-infectious pneumonitis.
  8. Patient with uncontrolled disease-related metabolic disorders (e.g., hypercalcemia, SIADH) or uncontrolled diabetes;
  9. Patient with uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or IV, uncontrolled hypertension, unstable heart disease (e.g., coronary artery disease with unstable angina or myocardial infarction within 6 months before study treatment administration).
  10. Patient with significant ECG abnormalities defined as any cardiac dysrhythmia (> Grade 2) (i.e., significant ventricular arrhythmia as persistent ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders as atrio-ventricular block 2 and 3, sino-atrial block) or baseline QT/QTc interval >480 milliseconds (ms).
  11. Patient with significant chronic liver disease (e.g., significant fibrosis, known cirrhosis) or active HBV or HCV infection; If HbsAg positive, an effective antiviral treatment to prevent hepatitis B reactivation is recommended.
  12. Patients with known Human Immunodeficiency Virus (HIV) infection or patients with an active infection requiring specific anti-infective therapy until all signs of infection have resolved, and this within 2 weeks prior to the first study treatment administration;
  13. Patient whose medical, psychological including alcohol or drug abuse, or surgical conditions are unstable and may affect the study completion and/or compliance and/or the ability to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03990233


Contacts
Layout table for location contacts
Contact: Bérangère Vasseur, MD +33 2 28 29 10 10 berangere.vasseur@ose-immuno.com

Locations
Layout table for location information
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Contact: Sandrine Aspeslagh, MD    +32 2 5413200    sandrine.aspeslagh@bordet.be   
France
Institut Bergonie Not yet recruiting
Bordeaux, France, 33076
Contact: Antoine Italiano, MD    +335 56 33 32 44    a.italiano@bordeaux.unicancer.fr   
Centre Oscar Lambret Not yet recruiting
Lille, France, 59000
Contact: Nicolas Penel, MD    +333 20 29 59 20    n-penel@o-lambret.fr   
Centre Léon Berard Recruiting
Lyon, France, 69373
Contact: Philippe Cassier, MD    +334 26 55 68 33    philippe.cassier@lyon.unicancer.fr   
Institut Claudius Regaud Recruiting
Toulouse, France, 31059
Contact: Jean-Pierre Delord, MD    +335 31 15 51 01    delord.jean-pierre@iuct-oncopole.fr   
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Aurelien Marabelle, MD    +331 42 11 55 92    aurelien.marabelle@gustaveroussy.fr   
Sponsors and Collaborators
OSE Immunotherapeutics
Boehringer Ingelheim

Layout table for additonal information
Responsible Party: OSE Immunotherapeutics
ClinicalTrials.gov Identifier: NCT03990233     History of Changes
Other Study ID Numbers: 1443-0001
2018-003830-34 ( EudraCT Number )
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by OSE Immunotherapeutics:
Checkpoint inhibitor (ICI)
SIRPα
Advanced solid tumors
Anti-PD-1