Phase 1
Completed N=65
BI 6727 Administered Intravenously Every 3 Weeks in Patients With Solid Tumours
Neoplasms
Source: ClinicalTrials.gov NCT02273388 ↗
Enrolled (actual)
65
Serious AEs
50.8%
Results posted
Oct 2023
Primary outcomePrimary: Maximum Tolerated Dose (MTD) — 400 Milligram (mg)
Summary
The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events. Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) |
400 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
1; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Relevant Abnormalities |
1; 2; 1; 1; 2; 3 | — |
| SECONDARY Number of Participants With Change in Eastern Cooperative Oncology Group (ECOG) Patient Performance Score |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Electrocardiogram (ECG) - QTcF Change From Baseline |
17.79; 13.23; 13.99; 6.84; 10.65; 7.08 | — |
| SECONDARY Vital Signs - Blood Pressure |
126; 124; 124; 112; 110; 130 | — |
| SECONDARY Vital Signs - Pulse Rate |
88; 80; 88; 92; 91; 88 | — |
| SECONDARY Number of Participants With Unconfirmed Best Overall Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Progression |
3; 3; 3; 2; 4; 3 | — |
| SECONDARY Maximum Concentration of BI 6727 in Plasma (Cmax) |
18.8; 50.7; 91.1; 169.0; 234.0; 470.0 | — |
| SECONDARY Time From Dosing to Maximum Concentration (Tmax) |
0.667; 0.750; 0.500; 0.884; 0.533; 1.00 | — |
| SECONDARY Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) |
149; 380; 778; 1270; 2140; 5670 | — |
| SECONDARY Area Under the Concentration-time Curve of BI 6727 in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point tz (AUC0-tz) |
101; 320; 636; 1110; 1800; 4780 | — |
| SECONDARY Terminal Rate Constant in Plasma (λz) |
0.00715; 0.00649; 0.00446; 0.00552; 0.00454; 0.00464 | — |
| SECONDARY Terminal Half-life of the Analyte in Plasma (t1/2) |
96.9; 107; 156; 126; 153; 149 | — |
| SECONDARY Mean Residence Time of BI 6727 in the Body After Intravenous Administration (MRT) |
113; 127; 174; 137; 164; 139 | — |
| SECONDARY Total Clearance of BI 6727 in the Plasma After Intravascular Adminstration (CL) |
1140; 876; 924; 918; 947; 547 | — |
| SECONDARY Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) |
7730; 6670; 9630; 7520; 9320; 4580 | — |
| SECONDARY Apparent Volume of Distribution During the Terminal Phase λz Following an Intravascular Dose (Vz) |
9530; 8100; 12400; 9980; 12500; 7070 | — |
| SECONDARY Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 24 Hours (Ae0-24) |
299; 493; 1580; 1170; 2120; NA | — |
| SECONDARY Amount of BI 6727 That is Eliminated in Urine From the Time Point 0 to Time Point 48 Hours (Ae0-48) |
379; 618; 2030; 1380; 2630; NA | — |
| SECONDARY Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 24 Hours (Fe0-24) |
3.10; 2.38; 3.65; 1.67; 1.74; NA | — |
| SECONDARY Fraction of BI 6727 Eliminated in Urine From Time Point 0 to Time Point 48 Hours (Fe0-48) |
3.75; 2.98; 4.71; 1.98; 2.16; NA | — |
| SECONDARY Renal Clearance of BI 6727 From the Time Point 0 to Time Point 24 Hours (CLr,0-24) |
106; 87.6; 127; 48.4; 56.7; NA | — |
| SECONDARY Renal Clearance of BI 6727 From the Time Point 0 to Time Point 48 Hours (CLr,0-48) |
99.8; 80.6; 118; 43.9; 51.6; NA | — |
Eligibility Criteria
Inclusion criteria
- Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
- Age 18 years or older
- Written informed consent consistent with ICH-GCP and local legislation
- Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score ¿ 2
- Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies (except alopecia)
The 18 additional patients recruited at the MTD must also meet the following criterion:
- Measurable tumour deposits (RECIST) by one or more techniques (CT, MRI)
Exclusion criteria
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
- Pregnancy or breastfeeding
- Active infectious disease or known chronic Hepatitis B/Hepatitis C infection
- Clinical evidence of active brain or leptomeningeal disease during the past 12 months
- Second malignancy currently requiring active therapy
- Absolute neutrophil count less than 1500 / mm3
- Platelet count less than 100 000 / mm3
- Bilirubin greater than 1.5 mg / dl (> 26 ¿mol / L, SI unit equivalent)
- Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
- Serum creatinine greater than 1.5 mg / dl (> 132 ¿mol / L, SI unit equivalent)
- Known history of relevant QT-prolongation, e.g. long QT-syndrome
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
- Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
- Chemo-, radio or immunotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
- Patients unable to comply with the protocol
- Active alcohol or drug abuse
Data sourced from ClinicalTrials.gov (NCT02273388). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.