Trial Outcomes & Findings for Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery (NCT NCT03433469)

Last Updated: 2025-01-31

Results Overview

Tumors that exhibit =\< 10% viable tumor will meet the criteria for a major pathological response. MPR will be determined in patients who receive at least one dose of study drug and become ineligible for surgery either because of disease progression or adverse event will be deemed not to have achieved MPR. The major pathological response rate will be reported with 95% confidence intervals.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2025-01-31

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Osimertinib) Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Overall Study STARTED	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Age, Customized 30-39 years old	1 Participants n=5 Participants
Age, Customized 40-49 years old	2 Participants n=5 Participants
Age, Customized 50-59 years old	4 Participants n=5 Participants
Age, Customized 60-69 years old	8 Participants n=5 Participants
Age, Customized 70-79 years old	9 Participants n=5 Participants
Age, Customized 80-89 years old	3 Participants n=5 Participants
Sex/Gender, Customized Female	20 Participants n=5 Participants
Sex/Gender, Customized Male	6 Participants n=5 Participants
Sex/Gender, Customized Not reported/Unknown/Declined to State	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Percentage of Participants With a Major Pathological Response (MPR)	14.8 percentage of participants Interval 5.9 to 32.5

SECONDARY outcome

Timeframe: Up to 70 days

The percentage of participants with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and by investigator's assessment will be determined from the time of treatment until surgery. The frequency and percentages of patients with a best ORR of CR, PR, SD, or PD will be determined. The ORR for each response type will be reported with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Objective Response Rates (ORR) Complete Response (CR)	0 percentage of participants Interval 0.0 to 12.5
Objective Response Rates (ORR) Partial Response	51.9 percentage of participants Interval 34.0 to 69.0
Objective Response Rates (ORR) Stable Disease	44.4 percentage of participants Interval 27.6 to 62.7
Objective Response Rates (ORR) Progressive Disease	3.7 percentage of participants Interval 0.2 to 18.3

SECONDARY outcome

Timeframe: Up to 5 years

DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median DFS with 95% confidence interval.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The 5-year DFS rate will be calculated as the percentage of patients who are disease free at 5 years. This will be calculated using the Kaplan-Meier method

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

5-year OS rate will be calculated using the Kaplan-Meier method . OS will be defined as the 1+ the number of days from surgical resection to death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year

Depth of response (DpR) will be defined as the percentage change in tumor burden by RECIST criteria at best response versus baseline imaging. DpR will be summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Median Percentage Change in Tumor Burden (Depth of Response)	-32 percent change Interval -40.0 to -18.0

SECONDARY outcome

Timeframe: Up to 1 year

The pCR is defined as absence of (0%) viable tumor present histologically in the resected tumor specimen

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Pathologic Complete Response Rate (pCR)	0 percentage of participants Interval 0.0 to 12.5

SECONDARY outcome

Timeframe: Up to 1 year

The percentage of participants with treatment-related adverse events will be reported. Adverse events will be classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Percentage of Participants With of Treatment-related Adverse Events (AEs)	100 percentage of participants

SECONDARY outcome

Timeframe: Up to 70 days

Rate of conversion from operable to non-operative will be recorded as rate of patients initially assessed as surgically resectable, who are subsequently unable to undergo surgical resection due to either treatment-related adverse events (AEs) or disease progression.

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=27 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Percentage of Participants Unable to Undergo Surgical Resection	11.1 percentage of participants Interval 3.9 to 28.1

SECONDARY outcome

Timeframe: Up to 1 year

Population: Three participants were deemed not to be surgical candidates by the investigator at the time of surgery following treatment and were excluded from the analysis.

Rate of surgical complications occurring prior to the end of treatment visit will be reported

Outcome measures

Outcome measures
Measure	Treatment (Osimertinib) n=24 Participants Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Percentage of Surgical Complications	62.5 percentage of participants Interval 42.7 to 78.8

Adverse Events

Treatment (Osimertinib)

Serious events: 3 serious events

Other events: 27 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Osimertinib) n=27 participants at risk Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Cardiac disorders Atrial fibrillation	3.7% 1/27 • Number of events 1 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.7% 1/27 • Number of events 1 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	3.7% 1/27 • Number of events 1 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.

Other adverse events

Other adverse events
Measure	Treatment (Osimertinib) n=27 participants at risk Participants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, participants may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Participants then undergo non-investigational surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Gastrointestinal disorders Diarrhea	48.1% 13/27 • Number of events 16 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Gastrointestinal disorders Nausea	25.9% 7/27 • Number of events 7 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Gastrointestinal disorders Dry mouth	14.8% 4/27 • Number of events 4 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Gastrointestinal disorders Abdominal distension	11.1% 3/27 • Number of events 4 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Gastrointestinal disorders Abdominal pain	11.1% 3/27 • Number of events 3 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Gastrointestinal disorders Constipation	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Skin and subcutaneous tissue disorders Dry Skin	18.5% 5/27 • Number of events 5 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	11.1% 3/27 • Number of events 5 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Respiratory, thoracic and mediastinal disorders Cough	22.2% 6/27 • Number of events 6 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.5% 5/27 • Number of events 5 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
General disorders Fatigue	29.6% 8/27 • Number of events 8 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
General disorders Fever	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Investigations Neutrophil count decreased	11.1% 3/27 • Number of events 5 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Investigations Alanine aminotransferase increased	7.4% 2/27 • Number of events 5 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Investigations Aspartate aminotransferase increased	7.4% 2/27 • Number of events 4 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Investigations Platelet count decreased	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Investigations White blood cell decreased	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Cardiac disorders Atrial fibrillation	11.1% 3/27 • Number of events 4 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Nervous system disorders Headache	11.1% 3/27 • Number of events 3 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Nervous system disorders Dizziness	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Eye disorders Blurred vision	11.1% 3/27 • Number of events 3 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Eye disorders Dry Eye	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Infections and infestations Paronychia	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Metabolism and nutrition disorders Anorexia	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Metabolism and nutrition disorders Hyponatremia	7.4% 2/27 • Number of events 4 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.
Musculoskeletal and connective tissue disorders Chest wall pain	7.4% 2/27 • Number of events 2 • Up to 1 year Collection for long term survival up to 5 years is still ongoing.

Additional Information

Dr. Collin M. Blakely, MD, PhD

University of California, San Francisco

Phone: (415) 502-6959

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place