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A Study to Test Different Doses of BI 836880 Combined With BI 754091 in Patients With Advanced Non-small Cell Lung Cancer Followed by Other Types of 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03468426
Recruitment Status : Suspended (Due to the current COVID-19 pandemic, the recruitment of new subjects is temporarily discontinued. Ongoing, randomised patients are managed per Trial Protocol.)
First Posted : March 16, 2018
Last Update Posted : April 6, 2020
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

PART 1:

Primary objective:

- To determine the Recommended Phase 2 Dose (RP2D) of BI 836880 in combination with BI 754091 in patients with locally advanced or metastatic non-squamous NSCLC who progressed during or after first line (in case of checkpoint inhibitor naïve patients) platinum-based therapy and patients who relapsed after completion of at least 2 cycles (in case of checkpoint inhibitor relapsing patients) of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy).

Secondary objective:

  • To provide safety data
  • To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first and fourth infusion cycle.

PART 2:

Primary objective:

- To assess anti-tumour activity of BI 836880 in combination with BI 754091 in patients with locally advanced or metastatic non-squamous NSCLC and other solid tumors

Secondary objective:

  • To provide safety data and further investigate clinical efficacy including disease control (DC), duration of objective response (DoR), progression free survival (PFS), and tumour shrinkage
  • To evaluate the basic pharmacokinetics of BI 836880 and BI 754091 during combination therapy after the first infusion cycle.

Condition or disease Intervention/treatment Phase
Non-squamous, Non-Small-Cell Lung Cancer Neoplasms Drug: BI 836880 Drug: BI 754091 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 245 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase Ib Dose Finding Study of BI 836880 in Combination With BI 754091 to Characterize Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy in Patients With Locally Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer and in Other Solid Tumors
Actual Study Start Date : May 3, 2018
Estimated Primary Completion Date : August 2, 2021
Estimated Study Completion Date : December 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: BI 836880 + BI 754091 Drug: BI 836880
intra-venous infusion

Drug: BI 754091
intra-venous infusion




Primary Outcome Measures :
  1. PART 1: Number of patients with Dose Limiting Toxicities (DLTs) within the first cycle of treatment [ Time Frame: Up to 3 weeks ]
  2. PART 2: Shrinkage estimator of objective response [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. PART 1:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 3 weeks ]
  2. PART 1: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle) [ Time Frame: Up to 504 hours after first and fourth infusion cycle ]
  3. PART 2:Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period [ Time Frame: Up to 3 weeks ]
  4. PART 2: Disease control (DC) [ Time Frame: Up to 3 years ]
  5. PART 2: Duration of objective response (DoR) [ Time Frame: Up to 3 years ]
  6. PART 2: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
  7. PART 2: Tumour shrinkage (in millimeters) [ Time Frame: Up to 3 years ]
  8. PART 2: AUC 0-504h (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 504 hours after the first and fourth infusion cycle) [ Time Frame: Up to 504 hours after first and fourth infusion cycle ]
  9. PART 1: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 12 weeks ]
  10. PART 1: tmax (time from dosing to maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 12 weeks ]
  11. PART 2: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 12 weeks ]
  12. PART 2: tmax (time from dosing to maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 12 weeks ]


Information from the National Library of Medicine

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

Inclusion Criteria:

Part 1:

  • Of full age (according to local legislation, usually ≥ 18 years) at screening.
  • Pathologically confirmed locally advanced or metastatic non-squamous NSCLC with PDL-1 expression available and >1% by IHC (as defined by the Pembrolizumab companion diagnostic test, determined by appropriate local pathology lab.
  • No previous treatment with check-point inhibitor. Or patients with checkpoint inhibitor based treatment as last therapy before entering the trial.
  • Documented disease progression or relapse (based on investigator's assessment) during or after completion of at least 2 cycles of platinum-based chemotherapy as first line treatment of Stage IIIB/IV non- squamous NSCLC or for checkpoint inhibitor experienced patients during or after completion of at least 2 cycles of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy). This includes patients relapsing within 6 months of completing (neo)adjuvant/curative-intent chemotherapy/CPI or chemoradiotherapy
  • At least one target lesion (outside the brain) that can be accurately measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
  • Lesion with a diameter ≥ 2cm assessed by radiologist as suitable for DCE-MRI evaluation (Mandatory in Part 1, optional in Part 2)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator
  • Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant.
  • Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
  • Availability and willingness to provide a fresh tumour tissue sample obtained at baseline, and after 2 cycles of treatment
  • Adequate organ function defined as all of the following (all screening labs should be performed at local lab within 10 days prior to treatment initiation)
  • 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, starting with the screening visit and through 6 months after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of contraception methods meeting these criteria is provided in the patient information Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study medication during the screening period. At the following visits according to the flowchart a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.

Part 1 & Part 2:

  • Of full age (according to local legislation, usually ≥ 18 years) at screening
  • At least one measurable target lesion outside the brain (excluding the glioblastoma patients), that can be accurately measured per RECIST 1.1
  • ECOG performance status ≤ 1 (For glioblastoma cohort Karnofsky status is applicable; see below)
  • Adequate organ function as all of the following (all screening labs should be performed at local lab within approximately 72 hours prior to treatment initiation)
  • Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in case no systemic antineoplastic therapy has been administered between the biopsy and C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy.
  • Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator
  • Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant.
  • Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
  • Male or female patients. Women of childbearing potential (WOCBP)2 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, for the entire duration of the trial treatment intake and for 6 months after the end of the trial treatment. A list of contraception methods meeting these criteria is provided in the patient information.

Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours during the screening period. At the following visits according to the flowchart, a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.- Further inclusion criteria apply

Exclusion criteria:

Part 1:

  • Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to drug product according to Investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of </= 10 mg/day prednisone).
  • Known immunodeficiency virus infection or an active hepatitis B or C virus infection.
  • History of severe hypersensitivity reactions to other mAbs.
  • Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of trial medication.
  • Current or prior treatment with any systemic anti-cancer therapy either within 28 days or a minimum of 5 half-lives, whichever is shorter before start of treatment.
  • Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
  • Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
  • Patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 480 ms).
  • Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II).

Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition >= 140 mmHg, systolic or >= 90 mmHg diastolic (with or without medication), measured according to Appendix 10.2.

  • LVEF < 50%
  • History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
  • Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
  • Patient with brain metastases that are symptomatic and/or require therapy.
  • Patients who require full-dose anticoagulation (according to local guidelines). No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment.
  • History of pneumonitis within the last 5 years
  • Patients who are under judicial protection and patients who are legally institutionalized.
  • Patients unable or unwilling to comply with protocol
  • Previous enrolment in this trial (Part 1 or Part 2).
  • Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
  • Women who are pregnant, nursing, or who plan to become pregnant in the trial

Part 2:

  • Known hypersensitivity to the trial drugs or their excipients or risk of allergic of anaphylactic reaction to drug product according to Investigator judgement (e.g. patient with history of anaphylactic reaction or autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of </= 10 mg/day prednisone).
  • Not more than one CPI based treatment regimen prior to entering study (eg. anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody) unless combination CPIs approved by the local regulatory agencies; For eg., Melanoma cohort (Cohort E).
  • Known HIV infection
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for patients in HCC cohorts; Cohorts F& G).
  • History of severe hypersensitivity reactions to other mAbs.
  • Immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of trial medication except for control of cerebral edema in case of recurrent glioblastoma (cohort D).
  • Current or prior treatment with any systemic anti-cancer therapy (including radiotherapy) either within 28 days or a minimum of 5 half-lives, whichever is shorter before start of treatment
  • Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the endpoints of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastrointestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
  • Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment, or planned surgical procedures during the trial period.
  • Patients with personal or family history of QT prolongation and/or long QT syndrome, or prolonged QTcF at baseline (> 480 ms).
  • Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > NYHA II).

Uncontrolled hypertension defined as: Blood pressure in rested and relaxed condition >= 140 mmHg, systolic or >= 90 mmHg diastolic (with or without medication), measured according to Appendix 10.2.

  • LVEF < 50%
  • History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis).
  • Known inherited predisposition to bleeding or to thrombosis in the opinion of the investigator.
  • Patient with brain metastases that are symptomatic and/or require therapy.
  • Patients who require full-dose anticoagulation (according to local guidelines).
  • No Vitamin K antagonist and other anticoagulation allowed; LMWH allowed only for prevention not for curative treatment.
  • History of pneumonitis (non-infectious) within the last 5 years
  • Patients who are under judicial protection and patients who are legally institutionalized.
  • Patients unable or unwilling to comply with protocol
  • Previous enrolment in this trial.
  • Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
  • Women who are pregnant, nursing, or who plan to become pregnant in the trial
  • UncontrolledSymptomatic pleural effusion, pericardial effusion, or ascites
  • Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib in 2nd line HCC cohort (Cohort F)
  • Has received a live vaccine within 30 days prior to the first dose of study drug
  • Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening
  • Further exclusion criteria apply

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): NCT03468426


Locations
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France
CTR Georges-François Leclerc
Dijon, France, 21079
HOP Timone
Marseille Cedex 5, France, 13385
INS Curie
Paris, France, 75005
CTR Eugène Marquis
Rennes Cedex, France, 35042
HOP Nord Laënnec
Saint-Herblain, France, 44800
HOP Civil
Strasbourg, France, 67091
Germany
Universitätsklinikum Augsburg
Augsburg, Germany, 86156
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, Germany, 01307
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55131
Universitätsklinikum Regensburg
Regensburg, Germany, 93053
Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, Korea, Republic of, 13620
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Spain
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Boehringer Ingelheim

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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03468426    
Other Study ID Numbers: 1336-0011
2017-001378-41 ( EudraCT Number )
First Posted: March 16, 2018    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms