BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour

The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin.

0=not maximum tolerated dose, 1=was maximum tolerated dose.

Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle.

Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0).

Tumour response was documented using appropriate techniques

Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria.

Tumour response was documented using appropriate techniques

Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria.

Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria.

Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first.

Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first.

Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0

Percentage of participants with serious adverse events (AEs)

Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE.

DLTs (i.e. significant AEs) per protocol were:

• drug related CTCAE grade 3 or 4 non haematological toxicity (except vomiting or diarrhoea responding to supportive treatment and ototoxicity)
• drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection
• drug related CTCAE Grade 4 thrombocytopenia
• drug related febrile neutropenia grade 3 (ANC<1000/mm³ and fever≥ 38.5°C)

Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.

Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.

Change from baseline in pulse rate at last value on treatment

Change from baseline in neutrophils with the maximum value on treatment

Change from baseline in platelets with the maximum value on treatment

Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils >=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets >=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline.

The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment.

Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment.

Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment.

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment.

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).