Trial Outcomes & Findings for BIBF 1120 in Combination With Pemetrexed in Advanced Non Small Cell Lung Cancer (NSCLC) (NCT NCT00979576)

Last Updated: 2025-03-06

Results Overview

Number of participants with dose limiting toxicity (DLT) in combination therapy of BIBF 1120 and pemetrexed during the first course

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

19 participants

Primary outcome timeframe

During the first course, 21 days

Results posted on

2025-03-06

Participant Flow

19 patients were enrolled in the study however one patient did not meet the inclusion criteria and therefore did not participate in the study.

Participant milestones

Participant milestones
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Combination Treatment Phase STARTED	3	6	9
Combination Treatment Phase COMPLETED	0	0	0
Combination Treatment Phase NOT COMPLETED	3	6	9
Combination Followed by Monotherapy STARTED	0	2	1
Combination Followed by Monotherapy COMPLETED	0	0	0
Combination Followed by Monotherapy NOT COMPLETED	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Combination Treatment Phase Progressive disease	3	1	5
Combination Treatment Phase Dose limiting toxicity	0	3	2
Combination Treatment Phase Adverse Event	0	2	2
Combination Followed by Monotherapy Progressive Disease	0	2	1

Baseline Characteristics

BIBF 1120 in Combination With Pemetrexed in Advanced Non Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	Total n=18 Participants Total of all reporting groups
Age, Continuous	61.0 years n=5 Participants	66.0 years n=7 Participants	64.0 years n=5 Participants	64.0 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	14 Participants n=4 Participants

PRIMARY outcome

Timeframe: During the first course, 21 days

Population: Treated set

Number of participants with dose limiting toxicity (DLT) in combination therapy of BIBF 1120 and pemetrexed during the first course

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Dose Limiting Toxicities	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days

Population: Treated set

Number of patients with adverse events according to worst Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE) or 5 (death related to AE).

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses Grade 1	0 participants	0 participants	1 participants
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses Grade 2	2 participants	1 participants	2 participants
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses Grade 3	1 participants	5 participants	5 participants
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses Grade 4	0 participants	0 participants	1 participants
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses Grade 5	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Every 6 weeks after start of study treatment until end of treatment, up to 992 days

Population: Treated set

Number of participants with complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Overall Response Rate Complete response	0 Participants	0 Participants	0 Participants
Overall Response Rate Partial response	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Every 6 weeks after start of study treatment until end of treatment, up to 992 days

Population: Treated set

Number of participants with complete response (CR), partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Disease Control Rate	2 Participants	4 Participants	6 Participants

SECONDARY outcome

Timeframe: From first study drug administration until PD or death, up to 1003 days

Population: Patients from the treated set who achieved disease control

Duration of disease control was defined as the time period from the first study drug administration to the progressive disease (PD) or death of patients, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=2 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=4 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Duration of Disease Control	248.5 Days Interval 162.0 to 335.0	228.5 Days Interval 168.0 to 587.0	149.0 Days Interval 121.0 to 1003.0

SECONDARY outcome

Timeframe: Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days

Population: Treated set

Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events which occurred in \>= 20% of patients

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Haemoglobin decreased	1 participants	1 participants	3 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Alanine aminotransferase increased	2 participants	6 participants	8 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Gamma-glutamyltransferase increased	2 participants	5 participants	8 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Aspartate aminotransferase increased	2 participants	5 participants	7 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Lymphocyte count decreased	2 participants	1 participants	2 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Neutrophil count decreased	2 participants	3 participants	4 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters White blood cell count decreased	2 participants	2 participants	3 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Blood alkaline phosphatase increased	0 participants	1 participants	4 participants
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters Blood albumin decreased	0 participants	1 participants	3 participants

SECONDARY outcome

Timeframe: 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1

Population: Pharmacokinetic (PK) set

Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
AUC0-inf of Nintedanib	105 ng*h/mL Geometric Coefficient of Variation 25.5	232 ng*h/mL Geometric Coefficient of Variation 60.5	323 ng*h/mL Geometric Coefficient of Variation 28.8

SECONDARY outcome

Timeframe: 5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1

Population: PK set

Maximum measured concentration of nintedanib in plasma (Cmax)

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Cmax of Nintedanib	20.5 ng/mL Geometric Coefficient of Variation 31.0	37.9 ng/mL Geometric Coefficient of Variation 71.7	55.1 ng/mL Geometric Coefficient of Variation 29.6

SECONDARY outcome

Timeframe: 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2

Population: PK set

Area under the concentration-time curve of pemetrexed in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=18 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
AUC0-inf of Pemetrexed Cycle 1	194000 ng*h/mL Geometric Coefficient of Variation 19.9	—	—
AUC0-inf of Pemetrexed Cycle 2 (N=11)	200000 ng*h/mL Geometric Coefficient of Variation 15.9	—	—

SECONDARY outcome

Timeframe: 5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2

Population: PK set

Maximum measured concentration of pemetrexed in plasma (Cmax)

Outcome measures

Outcome measures
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=18 Participants Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
Cmax of Pemetrexed Cycle 1	139000 ng/mL Geometric Coefficient of Variation 16.5	—	—
Cmax of Pemetrexed Cycle 2 (N=11)	149000 ng/mL Geometric Coefficient of Variation 15.4	—	—

Adverse Events

BIBF 1120 100 mg + Pemetrexed 500 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

BIBF 1120 150 mg + Pemetrexed 500 mg/m^2

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

BIBF 1120 200 mg + Pemetrexed 500 mg/m^2

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BIBF 1120 100 mg + Pemetrexed 500 mg/m^2 n=3 participants at risk Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 100 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 150 mg + Pemetrexed 500 mg/m^2 n=6 participants at risk Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 150 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.	BIBF 1120 200 mg + Pemetrexed 500 mg/m^2 n=9 participants at risk Treatments were administered in 21 day courses. Patients received pemetrexed 500 mg/m\^2 administered by intravenous infusion on day 1 and BIBF 1120 (nintedanib) 200 mg administered orally once on day 2 and twice daily (b.i.d.) from day 3 to day 21 in cycle 1 and b.i.d. from day 2 to day 21 in further cycles. In case that a patient had to discontinue pemetrexed, the patient was allowed to continue nintedanib monotherapy if the patient had been treated with the nintedanib combination therapy with pemetrexed for at least 4 courses.
General disorders Fatigue	33.3% 1/3 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	0.00% 0/6 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	0.00% 0/9 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days
Metabolism and nutrition disorders Hypercalcaemia	33.3% 1/3 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	0.00% 0/6 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	0.00% 0/9 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/3 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	0.00% 0/6 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days	11.1% 1/9 • Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days

Other adverse events

Additional Information

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