Trial Outcomes & Findings for Afatinib in NSCLC With HER2 Mutation (NCT NCT02597946)

Last Updated: 2025-02-19

Results Overview

Percentage of patients with objective response (OR) in part A according to RECIST 1.1. Objective Response defined as patients with tumour size reduction of a predefined amount using RECIST 1.1 in part A. Objective response included both confirmed Partial Response (PR) plus Complete Response (CR) as measured by Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) according to RECIST 1.1. Partial Response (PR): At least a 30% decrease in the sum of longest diameter (LD) of target lesions asking as reference the baseline sum LD. Complete Response (CR): Disappearance of all target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

CT Scan at Weeks 8 & 12 (for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment , ie., up to approximately 12 Months

Results posted on

2025-02-19

Participant Flow

Open label, single arm study, divided into 2 parts; Part A: All enrolled patients will receive afatinib monotherapy.Part B: Patients with more than 12 weeks clinical benefit in part A will receive afatinib once daily combined with paclitaxel once weekly.

No patients met the criteria to enter part B. Thus part B was not performed in this trial.

Participant milestones

Participant milestones
Measure	Afatinib 40 mg (Part A) Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Overall Study STARTED	18
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib 40 mg (Part A) Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Overall Study Withdrawal by Subject	1
Overall Study Progressive disease	16
Overall Study Other than above	1

Baseline Characteristics

Afatinib in NSCLC With HER2 Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Age, Continuous	53.6 Years STANDARD_DEVIATION 7.6 • n=99 Participants
Sex: Female, Male Female	12 Participants n=99 Participants
Sex: Female, Male Male	6 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	18 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: CT Scan at Weeks 8 & 12 (for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment , ie., up to approximately 12 Months

Population: Treated Set

Outcome measures

Outcome measures
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Percentage of Patients With Objective Response (OR) in Part A According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1	0.0 Percentage of participants

SECONDARY outcome

Timeframe: CT Scan at Weeks 8 & 12(for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment, ie up to approximately 12 Months

Population: Treated set

Percentage of patients with disease control (DC) in part A. Disease control defined as patients who have achieved confirmed complete response, partial response and stable disease as measured by CT scan or MRI according to RECIST 1.1 in part A. Tumour Response is based on clinical, radiological or other assessment. Clopper-Pearson method used for confidence limits. Partial Response (PR): At least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Complete Response (CR): Disappearance of all target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, taking as reference the baseline sum LD, nor sufficient increase to qualify for Progression (PD) taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Percentage of Patients With Disease Control (DC) in Part A	61.1 Percentage of participants Interval 35.7 to 82.7

SECONDARY outcome

Timeframe: From the date of starting treatment of afatinib to the date of disease progression or to the date of death, ie up to approximately 12 Months

Population: Treated set

Progression Free Survival (PFS) defined as the time from the date of starting treatment of afatinib to the date of disease progression per RECIST 1.1, or to the date of death no matter which happens first in part A. Median and 95% confidence interval (CI) are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Progression Free Survival (PFS) in Part A	2.76 Months Interval 1.87 to 4.6

SECONDARY outcome

Timeframe: From start of treatment of afatinib until death from any cause, ie up to approximately 12 Months

Population: Treated Set

Overall survival (OS) defined as the time from start of treatment of afatinib until death from any cause. Median and 95% CI are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Overall Survival (OS)	10.02 Months Interval 8.47 to 10.08

SECONDARY outcome

Timeframe: From the date of starting treatment of afatinib to the date of disease progression , ie up to approximately 12 Months

Population: Treated Set

Time to progression (TTP) defined as the time from the date of starting treatment of afatinib to the date of disease progression per RECIST 1.1 in part A. Median and 95% CI are calculated from an unadjusted Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Afatinib 40 mg (Part A) n=18 Participants Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Time to Progression (TTP) in Part A	2.76 Months Interval 1.87 to 4.6

SECONDARY outcome

Timeframe: CT Scan at Weeks 8 & 12(for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment, ie up to approximately 12 Months

Population: No patient had objective response and DoR was not analysed.

Duration of response (DoR) defined as the time from the first documented response PR or CR to the date of tumor progression evaluated according to RECIST 1.1 or death in part A. Partial Response (PR): At least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Complete Response (CR): Disappearance of all target lesions. No patient had objective response and DoR was not analysed.

Outcome measures

Outcome data not reported

Adverse Events

Afatinib 40 mg (Part A)

Serious events: 6 serious events

Other events: 18 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Afatinib 40 mg (Part A) n=18 participants at risk Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Infections and infestations Gastroenteritis	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Metabolism and nutrition disorders Decreased appetite	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Vascular disorders Thrombosis	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Respiratory, thoracic and mediastinal disorders Haemoptysis	11.1% 2/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
General disorders Malaise	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.

Other adverse events

Other adverse events
Measure	Afatinib 40 mg (Part A) n=18 participants at risk Patients were orally administered 40 milligram (mg) Afatinib film-coated tablets daily starting dose, once daily continuous (possible escalation to 50 mg, and reduction to 30 mg in the first step, and to 20 mg in the second step) until disease progression or intolerable toxicity or withdrawal of consent for any reason.
Infections and infestations Upper respiratory tract infection	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Infections and infestations Paronychia	11.1% 2/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Infections and infestations Lung infection	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Infections and infestations Myringitis	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Infections and infestations Pharyngitis	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Infections and infestations Urinary tract infection	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Blood and lymphatic system disorders Anaemia	22.2% 4/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Metabolism and nutrition disorders Decreased appetite	11.1% 2/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Metabolism and nutrition disorders Hyperglycaemia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Metabolism and nutrition disorders Hypocalcaemia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Psychiatric disorders Insomnia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Respiratory, thoracic and mediastinal disorders Productive cough	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Abdominal pain	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Mouth ulceration	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Stomatitis	11.1% 2/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Constipation	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Gingival swelling	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Nausea	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Tongue ulceration	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Vomiting	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Rash	33.3% 6/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Dermatitis acneiform	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Skin fissures	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Acne	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Pruritus generalised	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Skin and subcutaneous tissue disorders Skin exfoliation	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
General disorders Influenza like illness	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
General disorders Pyrexia	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Aspartate aminotransferase increased	22.2% 4/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Alanine aminotransferase increased	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Weight decreased	16.7% 3/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Blood creatinine increased	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Blood glucose increased	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Blood urea increased	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations Gamma-glutamyltransferase increased	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Investigations White blood cell count decreased	5.6% 1/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.
Gastrointestinal disorders Diarrhoea	66.7% 12/18 • From first drug administration until 30 days after the last dose, ie up to 272 days.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

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Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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