Trial Outcomes & Findings for A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC (NCT NCT05246514)

NCT ID: NCT05246514

Last Updated: 2025-08-28

Results Overview

Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 72 participants
• Primary outcome timeframe: At an average of approximately 14 months
• Results posted on: 2025-08-28

Participant Flow

Participant milestones

Measure	T-DXd Arm Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Overall Study STARTED	72
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	72

Reasons for withdrawal

Measure	T-DXd Arm Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Overall Study Ongoing in the study at data cut-off date	58
Overall Study Withdrawal by Subject	1
Overall Study Death	13

Baseline Characteristics

A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

Baseline characteristics by cohort

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Age, Continuous	57.4 Years STANDARD_DEVIATION 9.74 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 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	72 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	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At an average of approximately 14 months

Population: Full analysis set

Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
ICR-assessed ORR (Objective Response Rate)	58.3 Percentage of participants Interval 46.1 to 69.8

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: Full analysis set

Confirmed ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Investigator-assessed ORR (Objective Response Rate)	58.3 Percentage of participants Interval 46.1 to 69.8

SECONDARY outcome

Timeframe: At an average of approximately 14 months

Population: Full analysis set (patients with confirmed objective response included in the analysis)

DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
ICR-assessed and Investigator-assessed DoR (Duration of Response) ICR-assessed	NA Months Interval 6.1 to NA - Not calculated, estimate cannot be calculated as the median time frame was not reached. Insufficient number of participants with events for median and upper limit of 95% confidence interval.
ICR-assessed and Investigator-assessed DoR (Duration of Response) Investigator-assessed	9.0 Months Interval 7.2 to NA - Not calculated, estimate cannot be calculated. Insufficient number of participants with events for upper limit of 95% confidence interval.

SECONDARY outcome

Timeframe: Approximately 6 weeks

Population: Full analysis set

DCR is the percentage of participants who achieved confirmed CR, PR, or SD during study intervention.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
ICR-assessed and Investigator-assessed DCR (Disease Control Rate) ICR-assessed	91.7 Percentage of participants Interval 82.7 to 96.9
ICR-assessed and Investigator-assessed DCR (Disease Control Rate) Investigator-assessed	93.1 Percentage of participants Interval 84.5 to 97.7

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: Full analysis set

PFS is the time from date of enrolment until first objective radiographic tumour progression or death from any cause.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
ICR-assessed and Investigator-assessed PFS (Progression-free Survival) ICR-assessed	NA Months Interval 7.2 to NA - Not calculated, estimate cannot be calculated as the median PFS time was not reached. Insufficient number of participants with events for median and upper limit of 95% confidence interval.
ICR-assessed and Investigator-assessed PFS (Progression-free Survival) Investigator-assessed	10.8 Months Interval 7.2 to NA - Not calculated, estimate cannot be calculated. Insufficient number of participants with events for upper limit of 95% confidence interval.

SECONDARY outcome

Timeframe: An average of approximately 22 months

Population: Full analysis set

OS is the time from date of enrolment until death from any cause.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
OS (Overall Survival)	NA Months NA - Not calculated, estimate cannot be calculated as the median OS was not reached. Insufficient number of participants with events for median and lower and upper limits of 95% confidence interval.

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: Full analysis set

CNS-PFS is the time from date of enrolment until CNS tumour progression per RECIST 1.1 as assessed by ICR due to any cause in the absence of CNS progression.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
ICR-assessed CNS-PFS (Central Nervous System Progression-free Survival)	NA Months Interval 7.8 to NA - Not calculated, estimate cannot be calculated as the median CNS-PFS was not reached. Insufficient number of participants with events for median and upper limit of 95% confidence interval.

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: PK analysis set

Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Serum Concentrations of T-DXd Cycle 1 Pre-dose	NA μg/mL Geometric Coefficient of Variation NA NA - Not calculated, estimate cannot be calculated as too many values were below the lower limit of quantification.
Serum Concentrations of T-DXd Cycle 1 End of infusion	120.5 μg/mL Geometric Coefficient of Variation 18.33
Serum Concentrations of T-DXd Cycle 1 5 hour post-dose	106.1 μg/mL Geometric Coefficient of Variation 77.96
Serum Concentrations of T-DXd Cycle 2 Pre-dose	3.072 μg/mL Geometric Coefficient of Variation 121.6
Serum Concentrations of T-DXd Cycle 2 End of infusion	117.4 μg/mL Geometric Coefficient of Variation 18.79
Serum Concentrations of T-DXd Cycle 3 Pre-dose	5.262 μg/mL Geometric Coefficient of Variation 111.2
Serum Concentrations of T-DXd Cycle 3 End of infusion	120.9 μg/mL Geometric Coefficient of Variation 17.04
Serum Concentrations of T-DXd Cycle 4 Pre-dose	8.014 μg/mL Geometric Coefficient of Variation 60.69
Serum Concentrations of T-DXd Cycle 4 End of infusion	118.4 μg/mL Geometric Coefficient of Variation 18.44
Serum Concentrations of T-DXd Cycle 6 Pre-dose	9.046 μg/mL Geometric Coefficient of Variation 67.91
Serum Concentrations of T-DXd Cycle 8 Pre-dose	10.05 μg/mL Geometric Coefficient of Variation 68.29

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: PK analysis set

Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Serum Concentrations of Total Anti-HER2 Antibody Cycle 1 Pre-dose	NA ug/mL Geometric Coefficient of Variation NA NA - Not calculated, estimate cannot be calculated as too many values were below the lower limit of quantification.
Serum Concentrations of Total Anti-HER2 Antibody Cycle 1 End of infusion	127.5 ug/mL Geometric Coefficient of Variation 21.93
Serum Concentrations of Total Anti-HER2 Antibody Cycle 1 5 hour post-dose	118.0 ug/mL Geometric Coefficient of Variation 18.85
Serum Concentrations of Total Anti-HER2 Antibody Cycle 2 Pre-dose	2.866 ug/mL Geometric Coefficient of Variation 148.7
Serum Concentrations of Total Anti-HER2 Antibody Cycle 2 End of infusion	120.1 ug/mL Geometric Coefficient of Variation 39.66
Serum Concentrations of Total Anti-HER2 Antibody Cycle 3 Pre-dose	4.582 ug/mL Geometric Coefficient of Variation 126.4
Serum Concentrations of Total Anti-HER2 Antibody Cycle 3 End of infusion	125.9 ug/mL Geometric Coefficient of Variation 16.87
Serum Concentrations of Total Anti-HER2 Antibody Cycle 4 Pre-dose	6.974 ug/mL Geometric Coefficient of Variation 84.38
Serum Concentrations of Total Anti-HER2 Antibody Cycle 4 End of infusion	121.3 ug/mL Geometric Coefficient of Variation 16.80
Serum Concentrations of Total Anti-HER2 Antibody Cycle 6 Pre-dose	8.083 ug/mL Geometric Coefficient of Variation 95.47
Serum Concentrations of Total Anti-HER2 Antibody Cycle 8 Pre-dose	9.193 ug/mL Geometric Coefficient of Variation 87.45

SECONDARY outcome

Timeframe: An average of approximately 14 months

Population: PK analysis set

Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for DXd.

Outcome measures

Measure	T-DXd Arm n=72 Participants Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Serum Concentrations of DXd Cycle 4 End of infusion	2.139 ng/mL Geometric Coefficient of Variation 51.35
Serum Concentrations of DXd Cycle 1 Pre-dose	NA ng/mL Geometric Coefficient of Variation NA NA - Not calculated, estimate cannot be calculated as too many values were below the lower limit of quantification.
Serum Concentrations of DXd Cycle 1 End of infusion	5.384 ng/mL Geometric Coefficient of Variation 47.55
Serum Concentrations of DXd Cycle 1 5 hour post-dose	12.90 ng/mL Geometric Coefficient of Variation 69.38
Serum Concentrations of DXd Cycle 2 Pre-dose	0.1751 ng/mL Geometric Coefficient of Variation 119.4
Serum Concentrations of DXd Cycle 2 End of infusion	2.657 ng/mL Geometric Coefficient of Variation 70.96
Serum Concentrations of DXd Cycle 3 Pre-dose	0.2423 ng/mL Geometric Coefficient of Variation 110.6
Serum Concentrations of DXd Cycle 3 End of infusion	2.310 ng/mL Geometric Coefficient of Variation 50.12
Serum Concentrations of DXd Cycle 4 Pre-dose	0.3226 ng/mL Geometric Coefficient of Variation 53.71
Serum Concentrations of DXd Cycle 6 Pre-dose	0.3295 ng/mL Geometric Coefficient of Variation 58.92
Serum Concentrations of DXd Cycle 8 Pre-dose	0.3714 ng/mL Geometric Coefficient of Variation 57.45

Adverse Events

T-DXd Arm

Serious events: 33 serious events

Other events: 72 other events

Deaths: 13 deaths

Serious adverse events

Measure	T-DXd Arm n=72 participants at risk Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Gastrointestinal disorders Vomiting	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
General disorders Asthenia	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
General disorders Death	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
Hepatobiliary disorders Cholecystitis acute	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Infections and infestations Covid-19	6.9% 5/72 • Number of events 5 • An average of approximately 16 months
Infections and infestations Covid-19 pneumonia	5.6% 4/72 • Number of events 4 • An average of approximately 16 months
Blood and lymphatic system disorders Anaemia	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Infections and infestations Herpes zoster	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
Infections and infestations Pneumonia	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
Infections and infestations Pneumonia bacterial	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
Infections and infestations Upper respiratory tract infection	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Injury, poisoning and procedural complications Lumbar vertebral fracture	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Injury, poisoning and procedural complications Radiation pneumonitis	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Gastrointestinal disorders Abdominal distension	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Investigations Platelet count decreased	8.3% 6/72 • Number of events 7 • An average of approximately 16 months
Gastrointestinal disorders Ascites	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Nervous system disorders Brain oedema	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.8% 2/72 • Number of events 2 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Organising pneumonia	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.9% 5/72 • Number of events 5 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Vascular disorders Venous thrombosis limb	1.4% 1/72 • Number of events 1 • An average of approximately 16 months
Gastrointestinal disorders Gastritis	1.4% 1/72 • Number of events 1 • An average of approximately 16 months

Other adverse events

Measure	T-DXd Arm n=72 participants at risk Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.
Gastrointestinal disorders Vomiting	31.9% 23/72 • Number of events 49 • An average of approximately 16 months
General disorders Asthenia	15.3% 11/72 • Number of events 28 • An average of approximately 16 months
General disorders Fatigue	11.1% 8/72 • Number of events 12 • An average of approximately 16 months
General disorders Influenza like illness	6.9% 5/72 • Number of events 5 • An average of approximately 16 months
General disorders Malaise	8.3% 6/72 • Number of events 9 • An average of approximately 16 months
General disorders Pyrexia	5.6% 4/72 • Number of events 4 • An average of approximately 16 months
Infections and infestations Covid-19	36.1% 26/72 • Number of events 29 • An average of approximately 16 months
Infections and infestations Covid-19 pneumonia	6.9% 5/72 • Number of events 5 • An average of approximately 16 months
Blood and lymphatic system disorders Anaemia	56.9% 41/72 • Number of events 77 • An average of approximately 16 months
Infections and infestations Pneumonia	13.9% 10/72 • Number of events 10 • An average of approximately 16 months
Investigations Alanine aminotransferase increased	40.3% 29/72 • Number of events 48 • An average of approximately 16 months
Investigations Alpha hydroxybutyrate dehydrogenase increased	6.9% 5/72 • Number of events 9 • An average of approximately 16 months
Investigations Aspartate aminotransferase increased	56.9% 41/72 • Number of events 77 • An average of approximately 16 months
Investigations Bile acids increased	6.9% 5/72 • Number of events 10 • An average of approximately 16 months
Gastrointestinal disorders Abdominal distension	12.5% 9/72 • Number of events 18 • An average of approximately 16 months
Investigations Bilirubin conjugated increased	6.9% 5/72 • Number of events 6 • An average of approximately 16 months
Investigations Blood alkaline phosphatase increased	16.7% 12/72 • Number of events 17 • An average of approximately 16 months
Investigations Blood bilirubin increased	11.1% 8/72 • Number of events 10 • An average of approximately 16 months
Investigations Blood creatinine increased	6.9% 5/72 • Number of events 6 • An average of approximately 16 months
Investigations Blood lactate dehydrogenase increased	11.1% 8/72 • Number of events 10 • An average of approximately 16 months
Investigations Gamma-glutamyltransferase increased	25.0% 18/72 • Number of events 24 • An average of approximately 16 months
Investigations Lymphocyte count decreased	22.2% 16/72 • Number of events 36 • An average of approximately 16 months
Investigations Neutrophil count decreased	63.9% 46/72 • Number of events 163 • An average of approximately 16 months
Investigations Platelet count decreased	54.2% 39/72 • Number of events 81 • An average of approximately 16 months
Investigations Weight decreased	15.3% 11/72 • Number of events 14 • An average of approximately 16 months
Gastrointestinal disorders Abdominal pain upper	8.3% 6/72 • Number of events 12 • An average of approximately 16 months
Investigations Weight increased	6.9% 5/72 • Number of events 6 • An average of approximately 16 months
Investigations White blood cell count decreased	65.3% 47/72 • Number of events 191 • An average of approximately 16 months
Metabolism and nutrition disorders Decreased appetite	41.7% 30/72 • Number of events 50 • An average of approximately 16 months
Metabolism and nutrition disorders Hyperglycaemia	11.1% 8/72 • Number of events 10 • An average of approximately 16 months
Metabolism and nutrition disorders Hypertriglyceridaemia	9.7% 7/72 • Number of events 14 • An average of approximately 16 months
Metabolism and nutrition disorders Hyperuricaemia	12.5% 9/72 • Number of events 18 • An average of approximately 16 months
Metabolism and nutrition disorders Hypoalbuminaemia	29.2% 21/72 • Number of events 37 • An average of approximately 16 months
Metabolism and nutrition disorders Hypocalcaemia	22.2% 16/72 • Number of events 27 • An average of approximately 16 months
Metabolism and nutrition disorders Hypochloraemia	6.9% 5/72 • Number of events 5 • An average of approximately 16 months
Metabolism and nutrition disorders Hypokalaemia	22.2% 16/72 • Number of events 26 • An average of approximately 16 months
Metabolism and nutrition disorders Hyponatraemia	22.2% 16/72 • Number of events 19 • An average of approximately 16 months
Metabolism and nutrition disorders Hypophosphataemia	5.6% 4/72 • Number of events 5 • An average of approximately 16 months
Metabolism and nutrition disorders Hypoproteinaemia	8.3% 6/72 • Number of events 9 • An average of approximately 16 months
Psychiatric disorders Insomnia	11.1% 8/72 • Number of events 12 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Cough	19.4% 14/72 • Number of events 15 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 4/72 • Number of events 4 • An average of approximately 16 months
Gastrointestinal disorders Constipation	22.2% 16/72 • Number of events 26 • An average of approximately 16 months
Respiratory, thoracic and mediastinal disorders Productive cough	5.6% 4/72 • Number of events 4 • An average of approximately 16 months
Skin and subcutaneous tissue disorders Alopecia	13.9% 10/72 • Number of events 10 • An average of approximately 16 months
Skin and subcutaneous tissue disorders Rash	5.6% 4/72 • Number of events 5 • An average of approximately 16 months
Vascular disorders Hypertension	9.7% 7/72 • Number of events 16 • An average of approximately 16 months
Gastrointestinal disorders Diarrhoea	12.5% 9/72 • Number of events 11 • An average of approximately 16 months
Gastrointestinal disorders Nausea	59.7% 43/72 • Number of events 149 • An average of approximately 16 months

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place