Clinical trial NCT03972150: A Study to Find the Best Dose of BI 836880 Alone and in Combination With BI 754091 in Japanese Patients With Different Types of Advanced Cancer
Official title: An Open Label, Phase I Study of BI 836880 Monotherapy and Combination Therapy of BI 836880 and BI 754091 in Japanese Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 21
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is:

Part I

* To determine Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BI 836880 monotherapy Part II
* To determine MTD and/or RP2D of the combination therapy of BI 836880 and BI 754091

The secondary objectives are:

Part I

* To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 836880 as monotherapy Part II
* To document the safety and tolerability, and characterise PK of the combination therapy of BI 836880 and BI 754091


Eligibility criteria: Inclusion Criteria:

* Of legal age (according to local legislation) at screening. No upper limit.
* Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
* Male or female patients. Women of childbearing potential (WOCBP) 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 study treatment. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening.
* Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type). Measurable lesion not mandatory for participation in this trial.
* Patients with no therapy of proven efficacy, or who are not amenable to standard therapies.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
* Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or Common Terminology Criteria for Adverse Events (CTCAE) grade 1, except for alopecia (any grade), sensory peripheral neuropathy, must be ≤ CTCAE grade 2 or considered not clinically significant.
* Adequate organ function.
* Further inclusion criteria apply.

Exclusion criteria:

* 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 history of human immunodeficiency virus (HIV) infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date.
* Any of the following laboratory evidence of hepatitis virus infection.

  * Positive results of hepatitis B surface (HBs) antigen
  * Presence of hepatitis B core (HBc) antibody together with hepatitis virus B (HBV) Deoxyribonucleic acid (DNA)
  * Presence of hepatitis virus C (HCV) Ribonucleic acid (RNA) Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date.
* History of severe known 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.
* Any investigational or anti-tumour treatment within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initiation of trial 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 (Corrected QT interval by Fridericia) at screening (\>470 ms).
* Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure \>NYHA \[New York Heart Association\] class II).

Uncontrolled hypertension is defined as follows: Blood pressure in rested and relaxed condition ≥140 mmHg, systolic or ≥90 mmHg diastolic (with or without medication)

* Left Ventricular Ejection Fraction (LVEF) \<50% measured locally by echocardiography
* History of severe haemorrhagic 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.
* 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 progressive disease (PD) 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
* Patients who require full-dose anticoagulation (according to local guidelines). No Vitamin K antagonist and other anticoagulation allowed; Low Molecular Weight Heparin (LMWH) allowed only for prevention not for curative treatment.
* History (including current) of interstitial lung disease or pneumonitis within the last 5 years.
* 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
* Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled. (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant).
* Patients who were previously treated in this trial.
* Patients with haematological malignancies.
* Women who are pregnant, nursing, or who plan to become pregnant.
* Further exclusion criteria apply.

Primary outcomes:
measure: Part I and II: Maximum tolerated dose (MTD)
timeFrame: Up to 12 months
measure: Part I and II: Number of patients with Dose Limiting Toxicity (DLTs) in the Maximum tolerated dose (MTD) evaluation period
timeFrame: Up to 3 weeks
Secondary outcomes:
measure: Part I: Cmax: maximum measured concentration of BI 836880 in plasma
timeFrame: Up to 12 weeks
measure: Part I: AUC0-504h: area under the concentration-time curve of BI 836880 in plasma over the time interval from 0 to 504 hours
timeFrame: Up to 504 hours after first, second and fourth infusion cycle
measure: Part II: Cmax: maximum measured concentration of BI 836880 and BI 754091 in plasma
timeFrame: Up to 12 weeks
measure: Part II: AUC0-504h: area under the concentration-time curve of BI 836880 and BI 754091 in plasma over the time interval from 0 to 504 hours
timeFrame: Up to 504 hours after first and fourth infusion cycle
Other outcomes:
Locations:
city: Shizuoka, Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
Study officials:
References: