Trial Outcomes & Findings for Dasatinib and Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer With EGFR Mutations (NCT NCT02954523)

Last Updated: 2024-07-05

Results Overview

Number of patients with drug related adverse events (Dose Limiting Toxicities) on dasatinib when given in combination with osimertinib

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Cycle 1 (28 day cycle)

Results posted on

2024-07-05

Participant Flow

Study accrual terminated early and no subjects enrolled into the phase II portion of the study.

Participant milestones

Participant milestones
Measure	Phase IPhase I- Dasatinib Dose Level 2 Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70mg twice daily). There is no limit to the number of cycles a patient can receive.	Phase 1- DasatinibDose Level 1 Osimertinib(AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50mg twice daily). There is no limit to the number of cycles a patient can receive.	Phase 1- DasatinibDose Level -1 Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70mg once daily). There is no limit to the number of cycles a patient can receive.
Overall Study STARTED	3	6	1
Overall Study COMPLETED	3	6	1
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dasatinib and Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer With EGFR Mutations

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Cycle 1 (28 day cycle)

Number of patients with drug related adverse events (Dose Limiting Toxicities) on dasatinib when given in combination with osimertinib

Outcome measures

Outcome measures
Measure	Phase I- Dasatinib Dose Level 2 n=3 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=6 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),
Phase I : Number of Patients With Drug-related Adverse Events as Assessed by CTCAEv4.0	0 participants	3 participants	0 participants

PRIMARY outcome

Timeframe: 9 months

Population: Study close to accrual early. No participants enrolled in phase II.

The rate of patients non-responding (progressive disease or stable disease lasting 4 months or less) to the combination of osimertinib and dasatinib

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Population: Study close to accrual early. No participants enrolled in phase II.

Number of patients with treatment-related adverse events in the phase II study, who are treated at the same dose that has been selected based on the phase I part

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0 hour, 4 hours post dose

Population: Study Terminated early due to lack of enrollment.

To describe the concentration of osimertinib when administered with dasatinib. Blood is obtained from patients before each cycle and 4 hours after start of the first 2 cycles.

Outcome measures

Outcome measures
Measure	Phase I- Dasatinib Dose Level 2 n=6 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=3 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),
Concentration of Osimertinib in Blood (Cmax)	211.5 nM/mL Interval 166.0 to 314.0	355 nM/mL Interval 345.0 to 365.0	107 nM/mL Interval 107.0 to 107.0

SECONDARY outcome

Timeframe: 3 years

Determination of the time between the start of the experimental treatment and progression of the tumor

Outcome measures

Outcome measures
Measure	Phase I- Dasatinib Dose Level 2 n=6 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=3 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),
Progression-free Survival	24.7 months Interval 3.7 to 31.3	10.1 months Interval 4.5 to 16.7	10.5 months Interval 10.5 to 10.5

SECONDARY outcome

Timeframe: 47 months

From the date of start of the experimental treatment until the date of death from any cause, whichever came first, assessed up to 47 months.

Outcome measures

Outcome measures
Measure	Phase I- Dasatinib Dose Level 2 n=6 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=3 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),
Overall Survival	36.1 months Interval 23.5 to 46.6	16.9 months Interval 7.4 to 36.6	28.7 months Interval 28.7 to 28.7

SECONDARY outcome

Timeframe: 3 years

Determination of the duration of the response to the treatment, calculated from start of treatment in case of partial response and from the declaration of complete response in case of complete response. The end of the response will be when the tumor progresses

Outcome measures

Outcome measures
Measure	Phase I- Dasatinib Dose Level 2 n=6 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=3 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will begiven at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),
Duration of Response	27.8 months Interval 18.6 to 31.9	12.2 months Interval 8.4 to 15.9	8.7 months Interval 8.7 to 8.7

Adverse Events

Phase I- Dose Level 1

Serious events: 4 serious events

Other events: 6 other events

Deaths: 1 deaths

Phase I- Dose Level 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase I- Dose Level -1

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Chul Kim

Georgetown University

Phone: 12024442223

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I- Dasatinib Dose Level 2 n=3 Participants Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 2 (70 mg twice daily).	Phase 1- Dasatinib Dose Level 1 n=6 Participants Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level 1 (50 mg twice daily).	Phase 1- Dasatinib Dose Level -1 n=1 Participants Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally Level -1 (70 mg once daily),	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

Measure	Phase I- Dose Level 1 n=6 participants at risk Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at Level 1 (the starting dose - 50 mg twice daily), There is no limit to the number of cycles a patient can receive. Dasatinib: oral every day Osimertinib: oral every day	Phase I- Dose Level 2 n=3 participants at risk Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at Level 2 (70 mg twice daily). There is no limit to the number of cycles a patient can receive. Dasatinib: oral every day Osimertinib: oral every day	Phase I- Dose Level -1 n=1 participants at risk Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at Level -1 (70 mg once daily). There is no limit to the number of cycles a patient can receive. Dasatinib: oral every day Osimertinib: oral every day
Cardiac disorders Atrial fibrillation	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Infections and infestations Appendicitis	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Cardiac disorders Pericardial effusion	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Nervous system disorders Central nervous system necrosis	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Investigations Ejection fraction decreased	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Gastrointestinal disorders Hemorrhoidal hemorrhage	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Gastrointestinal disorders Intra-abdominal hemorrhage	0.00% 0/6 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	33.3% 1/3 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Infections and infestations Lung infection	16.7% 1/6 • Number of events 2 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Infections and infestations Nail infection	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Gastrointestinal disorders Rectal hemorrhage	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Infections and infestations Sepsis	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Vascular disorders Thromboembolic event	16.7% 1/6 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/3 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).
Vascular disorders Vascular disorders - Other, specify	0.00% 0/6 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	33.3% 1/3 • Number of events 1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).	0.00% 0/1 • Up to 6 years. Study Terminated early due to lack of enrollment. All subjects were analyzed together due to low accrual (too few people in each dose level).