Nintedanib low dose with docetaxel

Nintedanib medium dose with docetaxel

Nintedanib high dose with docetaxel

Nintedanib continuous high dose with docetaxel

Maximum tolerated dose (MTD) of nintedanib administered in combination with docetaxel. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 1 out of 6 subjects experiencing a DLT during the first treatment cycle i.e. the incidence of DLTs was no more than 17%. In case dose escalation reached dose level 3 (200 mg bid nintedanib administered without interruption on days of docetaxel infusion) and no more than 1 out of 6 subjects experienced a DLT during the first 28-day cycle at this dose level, dose level 3 was considered the MTD.

Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to nintedanib:

• Non-haematological drug-related Common Terminology Criteria for AEs (CTCAE) grade 3 or greater
• diarrhoea CTCAE grade 2 for >7 days despite supportive care
• nausea CTCAE grade 3 or greater despite supportive care
• vomiting CTCAE grade 2 or greater despite supportive care
• increase in Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) to CTCAE grade 3 or greater
• A increase in ALT and/or AST to CTCAE grade 2 or greater in conjunction with
• total bilirubin increase of CTCAE grade 1 or greater
• Platelets <50 000/mm3 with bleeding (CTCAE ≥3)
• neutropenia of any grade or duration accompanied by fever >38.5°C
• neutropenia grade 4 without fever of >7 days duration
• Inability to resume nintedanib dosing within 21 days after stopping due to toxicity.

In a treatment cycle of 28 days, 150 milligram (mg) nintedanib was administered orally twice a day with a dose interval of 12 hours with 250 milliliter (mL) of water after food intake except on the days of docetaxel infusion. Docetaxel (35 mg per square meter of body surface (mg/m2)) was administrated as a intravenous infusion over 60 minutes on Days 1, 8 and 15. The 28-day treatment cycles could be repeated until disease progression. In case of nintedanib-related adverse events, the dose of nintedanib was to be reduced to 100 mg twice a day, a second dose reduction was not allowed.

Maximum tolerated dose (MTD) of nintedanib administered in combination with docetaxel. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 1 out of 6 subjects experiencing a DLT during the first treatment cycle i.e. the incidence of DLTs was no more than 17%. In case dose escalation reached dose level 3 (200 mg bid nintedanib administered without interruption on days of docetaxel infusion) and no more than 1 out of 6 subjects experienced a DLT during the first 28-day cycle at this dose level, dose level 3 was considered the MTD.

Maximum tolerated dose (MTD) Evaluation Set: All subjects who received at least one dose of study medication and were evaluable for MTD determination.

In a treatment cycle of 28 days, 150 milligram (mg) nintedanib was administered orally twice a day with a dose interval of 12 hours with 250 milliliter (mL) of water after food intake except on the days of docetaxel infusion. Docetaxel (35 mg per square meter of body surface (mg/m2)) was administrated as a intravenous infusion over 60 minutes on Days 1, 8 and 15. The 28-day treatment cycles could be repeated until disease progression. In case of nintedanib-related adverse events, the dose of nintedanib was to be reduced to 100 mg twice a day, a second dose reduction was not allowed.