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A Trial to Find and Investigate a Safe Dose of a New Substance (BI 754091) for Patients With Solid Tumours

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ClinicalTrials.gov Identifier: NCT02952248
Recruitment Status : Active, not recruiting
First Posted : November 2, 2016
Last Update Posted : September 21, 2022
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The main objective of the dose-escalation part of the trial is to determine the safety and tolerability, and to determine the Maximum Tolerated Dose and/or the Recommended Phase 2 Dose (RP2D) of BI 754091 on the basis of patients with dose-limiting toxicities (DLTs) in patients with selected advanced solid malignancies. Safety and tolerability will be evaluated by monitoring the occurrence of adverse events (AEs), serious AEs (SAE), and laboratory parameter abnormalities, as well as changes to vital signs.

Secondary objectives are the determination of the PK profile of BI 754091 after single and multiple doses of BI 754091, and the preliminary assessment of antitumour activity.

In the dose-expansion part of the trial, the main objectives are to further assess the safety, efficacy, PK profile, and biomarkers of BI 754091 in tumours with specific tumour types and/or genetic mutations at the RP2D.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BI 754091 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics, and Efficacy of BI 754091 in Patients With Advanced Solid Tumours
Actual Study Start Date : November 21, 2016
Actual Primary Completion Date : April 30, 2021
Estimated Study Completion Date : December 1, 2022

Arm Intervention/treatment
Experimental: BI 754091 Drug: BI 754091

Primary Outcome Measures :
  1. Phase 1a: Number of patients experiencing Dose Limiting Toxicity (DLT) graded according to CTCAE Version 4.03 / 5.0, observed in the first cycle (3 weeks) in order to meet the objective of assessment of the Maximum-tolerated Dose of BI 754091. [ Time Frame: 3 Weeks ]
  2. Phase 1b: Number of patients with Dose Limiting Toxicity (DLT) observed during the entire treatment period. [ Time Frame: 357 days ]
  3. Phase 1b: Confirmed Objective Response (OR), defined as the best overall response of confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the Investigator. [ Time Frame: 357 days ]

Secondary Outcome Measures :
  1. Phase 1a: Maximum Measured Concentration (Cmax) of BI 754091 in plasma (if feasible) [ Time Frame: up to 387 days ]
  2. Phase 1a: Area Under the Concentration-Time Curve (AUC0-504) of BI 754091 in plasma over the time interval from 0 to 504 hours (if feasible) [ Time Frame: up to 504 hours ]
  3. Phase 1a: Confirmed Objective Response (OR) according to RECIST v1.1 as assessed by the Investigator) [ Time Frame: 357 days ]
  4. Phase 1a: Number of patients experiencing Dose Limiting Toxicities (DLT) from the start of treatment until end of treatment (in all cycles) as assessed approximately every 3 weeks. [ Time Frame: 357 days ]
  5. Phase 1b: Progression-free survival (PFS) defined from date of start of BI 754091 to the date of disease progression or death, whichever is earlier, according to RECIST v1.1 as assessed by the Investigator [ Time Frame: 357 days ]
  6. Phase 1b: Percentage of Subjects with Adverse Events (AE)s. [ Time Frame: 387 days ]
  7. Phase 1b: Percentage of Subjects with Serious Adverse Events (SAE)s. [ Time Frame: 387 days ]
  8. Phase 1b: Percentage of Subjects with Clinical Relevant Abnormalities in Vital Signs, Laboratory Evaluations or Electrocardiogram parameters (note that clinically relevant abnormalities are those which have to be reported by the investigator as AEs). [ Time Frame: 387 days ]

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

Inclusion Criteria:

  • Provision of signed and dated, written Informed Consent Form (ICF) prior to any trial-specific procedures, sampling, or analyses. If a patient declines to participate in the voluntary pharmacogenetics component of the trial, he/she will not be excluded from other aspects of the trial.
  • Patients ≥18 years of age at the time of signature of the ICF
  • Phase Ia (dose-escalation)

    • patients with a histologically confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type).
    • patients who have received all therapy known to confer clinical benefit (including anti-PD-1 or anti-PDL1 therapies, if relevant), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Patients with anti- PD-1 or anti-PDL1 experience must have a minimum of 60 days between the last dose of the previous anti PD-1/PD-L1 and Cycle 1 Day 1 of BI 754091 treatment.
    • Patients may agree to provide optional paired biopsies.
  • Phase Ib (dose expansion)

    • patients with a histologically confirmed diagnosis of select advanced, unresectable, and/or metastatic solid tumours with either 1) high tumor mutation excluding high microsatellite instability or 2) refractory squamous cell cervical, anal and skin tumors, or 3) recurrent vaginal or vulvar squamous cell carcinoma.
    • All patients must have measurable lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 must have at least 1 tumour lesion amenable to biopsy, and must be medically fit and willing to undergo a biopsy before first treatment and, unless clinically contraindicated, after 6 weeks on therapy
    • patients who are anti-PD-1 and anti-PDL-1naïve but have failed conventional treatment (excluding anti-PD-1 treatment), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies.
  • Eastern Cooperative Oncology Group (ECOG) score: 0 to 1
  • Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
  • Females of child-bearing potential willing to use adequate contraceptive measures from the time of screening until 6 months after trial discontinuation, who are not or will not be breast feeding, and agree to have pregnancy tests prior to the start of dosing and at regular visits during the trial. Females not of childbearing potential must have evidence of such by fulfilling one of the following criteria at screening:

    • Post-menopausal: defined as more than 50 years-of-age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
    • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy
    • Women under 50 years-of-age would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
    • For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary. Acceptable highly effective methods of contraception include total sexual abstinence when this is in line with the preferred and usual lifestyle of the study participant (periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception), an intrauterine device or intrauterine hormone-releasing system, bilateral tubal ligation, and vasectomised partner (with post-vasectomy proof of absence of sperm)
  • Further inclusion criteria apply

Exclusion criteria:

  • Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 months after screening, e.g.,hip replacement
  • Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
  • Previous enrolment in this trial
  • Any investigational or anti-tumour treatment within 4 weeks or 5 half-life period (whichever is shorter) prior to the initial administration of BI 754091.
  • Presence of other active invasive cancers other than the one treated in this trial within 5 years prior to screening, with the exception of appropriately treated basal-cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or other local tumours considered cured by local treatment.
  • Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of Progression of Disease by imaging for at least 4 weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases
  • Inadequate organ function or bone marrow reserve as demonstrated by the following laboratory values:

    • Absolute neutrophil count <1.5 x 10^9/L (<1500/mm3)
    • Platelet count <100 x 10^9/L
    • Haemoglobin <90 g/L (<9 g/dL)
    • Alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
    • Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
    • Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN
    • Creatinine >1.5 times ULN or creatinine clearance <50 mL/min (measured or calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTc) >470 msec
    • Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting Electrocardiograms, e.g., complete left bundle branch block, third degree heart block
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
    • Ejection fraction (EF) <55% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram [ECHO], multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
  • History of pneumonitis within the last 5 years
  • History of severe hypersensitivity reactions to other monoclonal Antibodies
  • Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of BI 754091
  • Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy
  • Known history of human immunodeficiency virus infection or an active hepatitis B or C virus infection. HIV infection is allowed for patients in cohort 6 (cervical/anal squamous) and cohort 7 (vulvar)
  • Interstitial lung disease
  • Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes him/her an unreliable trial subject, unlikely to complete the trial, or unable to comply with the protocol procedures.

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): NCT02952248

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United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Illinois
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Greenville Health System
Greenville, South Carolina, United States, 29605
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, Ontario
Juravinski Cancer Centre - Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, Canada, H2X 0A9
United Kingdom
Sarah Cannon Research Institute
London, United Kingdom, W1G 6AD
The Christie Hospital
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02952248    
Other Study ID Numbers: 1381.1
2017-005043-33 ( EudraCT Number )
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing