A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations - DPT01

Study identifier:D967MC00001

ClinicalTrials.gov identifier:NCT04639219

EudraCT identifier:2020-002368-30

CTIS identifier:N/A

Recruitment Complete

Official Title

A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology

Medical condition

Advanced solid tumors with HER2 mutation,eg:colorectal,urothelial,gastric, hepatobiliary,endometrial,melanoma,ovarian,cervical,salivary gland,pancreatic,breast

Phase

Phase 2

Healthy volunteers

Study drug

Trastuzumab deruxtecan

Sex

All

Actual Enrollment

102

Study type

Interventional

Age

18 Years - 120 Years

Date

Study Start Date: 30 Dec 2020

Primary Completion Date: 25 Jan 2023

Estimated Study Completion Date: 14 Jul 2026

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2025 by AstraZeneca

Collaborators

Daiichi Sankyo Co., Ltd.

Inclusion and exclusion criteria

Location

Research Site

Houston, TX, United States, 77030

Location

Research Site

New York, NY, United States, 10021

Location

Research Site

Boston, MA, United States, 02115

Location

Research Site

Madrid, Spain, 28041

Location

Research Site

Sevilla, Spain, 41013

Location

Research Site

Seoul, Republic of Korea, 06351

Location

Research Site

Muncie, IN, United States, 47303

Location

Research Site

Fairfax, VA, United States, 22031

Arms	Assigned Interventions
Experimental: T-DXd T-DXd monotherapy	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This Phase II multicenter, open-label study was conducted in participants with unresectable and/or metastatic solid tumors harboring human epidermal growth factor receptor 2 (HER2) activating mutations regardless of tumor histology at 29 investigational sites in 9 countries. First participant was enrolled on 30 Dec 2020, last participant was enrolled on 24 May 2022 and data cut-off (DCO) date was 25 Jan 2023.

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

This Phase II multicenter, open-label study was conducted in participants with unresectable and/or metastatic solid tumors harboring human epidermal growth factor receptor 2 (HER2) activating mutations regardless of tumor histology at 29 investigational sites in 9 countries. First participant was enrolled on 30 Dec 2020, last participant was enrolled on 24 May 2022 and data cut-off (DCO) date was 25 Jan 2023.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a screening period (up to 28 days), treatment period until progressive disease (PD) and a follow-up period for participants who discontinued study treatment due to PD or other reason. A total of 102 participants received treatment in this study.

Reporting Groups

	Description
Trastuzumab Deruxtecan (T-DXd)	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 milligram/kilogram (mg/kg) via intravenous (IV) infusion on Day 1 of each cycle (21 days), every 3 weeks until response evaluation criteria in solid tumors (RECIST) version (v) 1.1 -defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Participant Flow: Overall Study

	Trastuzumab Deruxtecan (T-DXd)
STARTED	102
COMPLETED	33
NOT COMPLETED	69
Withdrawal by Subject	8
Lost to Follow-up	6
Death	55

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The Full Analysis Set (FAS) consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Baseline Measures

	T-DXd
Number of Participants [units: Participants]	102
Age Continuous [units: years] Mean ± Standard Deviation	64.2 ± 10.29
Sex: Female, Male [units: participants]
Female	62
Male	40
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	38
Native Hawaiian or Other Pacific Islander	0
Black or African American	2
White	51
More than one race	0
Unknown or Not Reported	11
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	2
Not Hispanic or Latino	91
Unknown or Not Reported	9

Outcome Measures

1. Primary Outcome Measure: Confirmed Overall Response Rate (ORR) as per RECIST v1.1 Using Independent Central Review (ICR) [ Time Frame: Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) ]

Measure Type	Primary
Measure Name	Confirmed Overall Response Rate (ORR) as per RECIST v1.1 Using Independent Central Review (ICR)
Measure Description	Confirmed ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR), as determined by ICR per RECIST v1.1. A CR was defined as disappearance of all target lesions (TLs) and PR was defined as at least a 30% decrease in the sum of the diameters (dms) of TL, taking as reference the baseline sum of diameters as long as criteria for PD were not met. An ICR of all radiological imaging data was carried out using RECIST v1.1. All images were collected centrally. The imaging scans were reviewed by 2 independent radiologists and were adjudicated, if required.
Time Frame	Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Confirmed Overall Response Rate (ORR) as per RECIST v1.1 Using Independent Central Review (ICR) [units: percentage of participants] Number (95% Confidence Interval)	29.4 (20.8 to 39.3)

No statistical analysis provided for Confirmed Overall Response Rate (ORR) as per RECIST v1.1 Using Independent Central Review (ICR)

2. Secondary Outcome Measure: Duration of Response (DoR) as per RECIST v1.1 Using ICR and Investigator Assessment [ Time Frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) ]

Measure Type	Secondary
Measure Name	Duration of Response (DoR) as per RECIST v1.1 Using ICR and Investigator Assessment
Measure Description	DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (date of progression-free survival [PFS] event or censoring – date of first response + 1). The DoR was calculated using Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment. Participants with response were evaluated.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Duration of Response (DoR) as per RECIST v1.1 Using ICR and Investigator Assessment [units: months] Median (Inter-Quartile Range)
DoR by ICR	NA (6.8 to NA) ^[1]
DoR by Investigator assessment	11.0 (6.9 to 18.1)

No statistical analysis provided for Duration of Response (DoR) as per RECIST v1.1 Using ICR and Investigator Assessment

3. Secondary Outcome Measure: Disease Control Rate (DCR) as per RECIST v1.1 Using ICR and Investigator Assessment [ Time Frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) ]

Measure Type	Secondary
Measure Name	Disease Control Rate (DCR) as per RECIST v1.1 Using ICR and Investigator Assessment
Measure Description	DCR at 6 weeks was defined as the percentage of participants who had the best objective response (BoR) of confirmed CR or PR, or who had stable disease (SD) (without subsequent cancer therapy), for at least 5 weeks after first dose of study treatment. DCR at 12 weeks was defined as the percentage of patients who had the BoR of confirmed CR or PR, or who had SD (without subsequent cancer therapy), for at least 11 weeks after first dose of study treatment. CR was defined as disappearance of all TL and PR was defined as at least a 30% decrease in sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (>=20% increase in sum of dms of TLs and an absolute increase of >=5 millimeters, taking as reference smallest sum of dms since treatment started including baseline sum of dms). CI was calculated using Clopper-Pearson method.
Time Frame	Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Disease Control Rate (DCR) as per RECIST v1.1 Using ICR and Investigator Assessment [units: percentage of participants] Number (95% Confidence Interval)
DCR at 6 weeks by ICR	75.5 (66.0 to 83.5)
DCR at 6 weeks by Investigator assessment	70.6 (60.7 to 79.2)
DCR at 12 weeks by ICR	53.9 (43.8 to 63.8)
DCR at 12 weeks by Investigator assessment	55.9 (45.7 to 65.7)

No statistical analysis provided for Disease Control Rate (DCR) as per RECIST v1.1 Using ICR and Investigator Assessment

4. Secondary Outcome Measure: PFS as per RECIST v1.1 Using ICR and Investigator Assessment [ Time Frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) ]

Measure Type	Secondary
Measure Name	PFS as per RECIST v1.1 Using ICR and Investigator Assessment
Measure Description	PFS was defined as the time from first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from assigned therapy or received another anti-cancer therapy prior to progression (i.e. date of PFS event or censoring – date of first dose + 1). PFS was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.
Time Frame	Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
PFS as per RECIST v1.1 Using ICR and Investigator Assessment [units: months] Median (95% Confidence Interval)
PFS by ICR	5.4 (2.7 to 7.1)
PFS by Investigator assessment	4.4 (2.8 to 5.6)

No statistical analysis provided for PFS as per RECIST v1.1 Using ICR and Investigator Assessment

5. Secondary Outcome Measure: Percentage of Participants Alive and Progression-Free at 6 and 12 Months as per RECIST v1.1 Using ICR and Investigator Assessment [ Time Frame: At Months 6 and 12 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Alive and Progression-Free at 6 and 12 Months as per RECIST v1.1 Using ICR and Investigator Assessment
Measure Description	Percentage of participants alive and progression-free at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.
Time Frame	At Months 6 and 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Percentage of Participants Alive and Progression-Free at 6 and 12 Months as per RECIST v1.1 Using ICR and Investigator Assessment [units: percentage of participants] Number (95% Confidence Interval)
PFS rate at 6 months by ICR	41.4 (30.8 to 51.6)
PFS rate at 6 months by Investigator assessment	37.7 (28.1 to 47.2)
PFS rate at 12 months by ICR	30.9 (20.6 to 41.8)
PFS rate at 12 months by Investigator assessment	26.5 (17.2 to 36.7)

No statistical analysis provided for Percentage of Participants Alive and Progression-Free at 6 and 12 Months as per RECIST v1.1 Using ICR and Investigator Assessment

6. Secondary Outcome Measure: Confirmed ORR as per RECIST v1.1 Using Investigator Assessment [ Time Frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) ]

Measure Type	Secondary
Measure Name	Confirmed ORR as per RECIST v1.1 Using Investigator Assessment
Measure Description	Confirmed ORR was defined as the percentage of participants who had a confirmed CR or PR as determined by investigator per RECIST v1.1. A CR was defined as disappearance of all TLs and PR was defined as >=30% decrease in the sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met.
Time Frame	Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Confirmed ORR as per RECIST v1.1 Using Investigator Assessment [units: percentage of participants] Number (95% Confidence Interval)	32.4 (23.4 to 42.3)

No statistical analysis provided for Confirmed ORR as per RECIST v1.1 Using Investigator Assessment

7. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: From the date of first treatment administration up to death, approximately 24 months ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	OS was defined as the time from the date of first dose of study treatment administration until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy (i.e. date of death or censoring – date of first dose + 1). OS was calculated using the Kaplan-Meier technique. CI for median OS derived based on the Brookmeyer-Crowley method.
Time Frame	From the date of first treatment administration up to death, approximately 24 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Overall Survival (OS) [units: months] Median (95% Confidence Interval)	10.9 (8.3 to 14.9)

No statistical analysis provided for Overall Survival (OS)

8. Secondary Outcome Measure: Percentage of Participants Alive at 6 and 12 Months [ Time Frame: At Months 6 and 12 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Alive at 6 and 12 Months
Measure Description	Percentage of participants alive at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.
Time Frame	At Months 6 and 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	102
Percentage of Participants Alive at 6 and 12 Months [units: percentage of participants] Number (95% Confidence Interval)
Survival rate at 6 months	67.6 (57.4 to 75.9)
Survival rate at 12 months	46.3 (35.7 to 56.3)

No statistical analysis provided for Percentage of Participants Alive at 6 and 12 Months

9. Secondary Outcome Measure: Serum Concentrations of T-DXd and Total Anti-HER2 Antibody [ Time Frame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days) ]

Measure Type	Secondary
Measure Name	Serum Concentrations of T-DXd and Total Anti-HER2 Antibody
Measure Description	Serum samples were collected at specified timepoints to determine serum concentrations of T-DXd and total anti-HER2 antibody.
Time Frame	Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) Analysis set consisted of all participants who received at least 1 dose of study treatment and had at least 1 post-dose evaluable PK data point. The population was defined by the study pharmacokineticist and the statistician prior to any PK analyses being performed. Only those participants with data available are reported.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	100
Serum Concentrations of T-DXd and Total Anti-HER2 Antibody [units: microgram/milliliter (mL)] Mean (Standard Deviation)
T-DXd: Cycle 1: Pre-infusion	NA (NA)^[1]
T-DXd: Cycle 1: 15 minutes post-infusion	116.5 (50.8)
T-DXd: Cycle 1: 5 hours post-infusion	115.4 (30.5)
T-DXd: Cycle 2: Pre-infusion	11.2 (74.1)
T-DXd: Cycle 2: 15 minutes post-infusion	132.2 (101.5)
T-DXd: Cycle 4: Pre-infusion	7.7 (9.1)
T-DXd: Cycle 4: 15 minutes post-infusion	121.7 (40.1)
Total anti-HER2 antibody: Cycle 1: Pre-infusion	NA (NA)^[1]
Total anti-HER2 antibody: Cycle 1: 15 minutes post-infusion	123.8 (52.8)
Total anti-HER2 antibody: Cycle 1: 5 hours post-infusion	122.1 (42.1)
Total anti-HER2 antibody: Cycle 2: Pre-infusion	6.2 (12.4)
Total anti-HER2 antibody: Cycle 2: 15 minutes post-infusion	144.4 (115.4)
Total anti-HER2 antibody: Cycle 4: Pre-infusion	9.9 (5.7)
Total anti-HER2 antibody: Cycle 4: 15 minutes post-infusion	122.1 (37.3)

No statistical analysis provided for Serum Concentrations of T-DXd and Total Anti-HER2 Antibody

10. Secondary Outcome Measure: Serum Concentrations of Deruxtecan (MAAA-1181a) [ Time Frame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days) ]

Measure Type	Secondary
Measure Name	Serum Concentrations of Deruxtecan (MAAA-1181a)
Measure Description	Serum samples were collected at specified timepoints to determine serum concentrations of MAAA-1181a.
Time Frame	Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) Analysis set consisted of all participants who received at least 1 dose of study treatment and had at least 1 post-dose evaluable PK data point. The population was defined by the study pharmacokineticist and the statistician prior to any PK analyses being performed. Only those participants with data available are reported.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	100
Serum Concentrations of Deruxtecan (MAAA-1181a) [units: ng/mL] Mean (Standard Deviation)
MAAA-1181a: Cycle 1: Pre-infusion
MAAA-1181a: Cycle 1: 15 minutes post-infusion	4.7 (2.9)
MAAA-1181a: Cycle 1: 5 hours post-infusion	10.5 (5.1)
MAAA-1181a: Cycle 2: Pre-infusion	0.2 (0.1)
MAAA-1181a: Cycle 2: 15 minutes post-infusion	2.2 (1.5)
MAAA-1181a: Cycle 4: Pre-infusion	0.3 (0.2)
MAAA-1181a: Cycle 4: 15 minutes post-infusion	1.5 (0.9)

No statistical analysis provided for Serum Concentrations of Deruxtecan (MAAA-1181a)

11. Secondary Outcome Measure: Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd [ Time Frame: Up to approximately 24 months ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd
Measure Description	Blood samples were collected to evaluate the presence of ADAs for T-DXd using validated assays. ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence was defined as the percentage of participants who were evaluable for ADA and were treatment-emergent ADA-positive. Treatment-emergent ADA was defined as either treatment-induced (baseline ADA negative, post-baseline ADA positive) or treatment-boosted ADA. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to >=2 fold during the study period. Persistently positive was defined as >=2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive was defined as having >=1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.
Time Frame	Up to approximately 24 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the ADA-evaluable set consisted of all participants in the Safety Analysis set (SAF- All participants who received at least 1 dose of study treatment) with a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result.

Reporting Groups

	Description
T-DXd	Participants harboring tumors with specific HER2 activating mutations received T-DXd 5.4 mg/kg via IV infusion on Day 1 of each cycle (21 days), every 3 weeks until RECIST v1.1-defined PD, withdrawal of consent, or until any other of the discontinuation criteria was met.

Measured Values

	T-DXd
Number of Participants Analyzed [units:participants]	96
Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd [units: percentage of participants]
ADA positive at any visit (ADA prevalence)	2.1
ADA incidence	0
Treatment-emergent ADA positive	0
Treatment-boosted ADA positive	0
Persistently positive ADA	0
Transiently positive ADA	0

No statistical analysis provided for Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd

Serious Adverse Events

Time Frame	Treatment-emergent adverse events were collected from start of first dose of study treatment up to and including 47 days following the date of last dose of study treatment or before the initiation of first subsequent anti-cancer therapy following discontinuation of study treatment (whichever occurred first), up to DCO date of 25 Jan 2023 (approximately 24 months)
Additional Description	The SAF consisted of all participants who received at least 1 dose of study treatment.

Reporting Groups

	Description
T-DXd	Description (Arm-group)

Serious Adverse Events

T-DXd

Total, serious adverse events

# participants affected / at risk

36/102 (35.29%)

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Injury, poisoning and procedural complications

Ankle fracture¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Metabolism and nutrition disorders

Shock hypoglycaemic¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Eye disorders

Ulcerative keratitis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Reproductive system and breast disorders

Prostatitis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

4/102 (3.92%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Vascular disorders

Lymphoedema¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Anal fistula¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Duodenal ulcer¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Haematemesis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Obstruction gastric¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

General disorders and administration site conditions

Complication associated with device¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

General disorders and administration site conditions

General physical health deterioration¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Hepatobiliary disorders

Biliary obstruction¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Hepatobiliary disorders

Cholangitis¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Infections and infestations

Biliary tract infection¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

COVID-19 pneumonia¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Localised infection¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Meningitis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Peritonitis¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Pneumocystis jirovecii pneumonia¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/102 (1.96%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

1/102 (0.98%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 25.1

Other Adverse Events

Time Frame	Treatment-emergent adverse events were collected from start of first dose of study treatment up to and including 47 days following the date of last dose of study treatment or before the initiation of first subsequent anti-cancer therapy following discontinuation of study treatment (whichever occurred first), up to DCO date of 25 Jan 2023 (approximately 24 months)
Additional Description	The SAF consisted of all participants who received at least 1 dose of study treatment.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
T-DXd	Description (Arm-group)

Other Adverse Events

T-DXd

Total, other (not including serious) adverse events

# participants affected / at risk

96/102 (94.12%)

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

14/102 (13.73%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

18/102 (17.65%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

15/102 (14.71%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

13/102 (12.75%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

24/102 (23.53%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

8/102 (7.84%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

8/102 (7.84%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/102 (7.84%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

35/102 (34.31%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

13/102 (12.75%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

11/102 (10.78%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

12/102 (11.76%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

18/102 (17.65%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

6/102 (5.88%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

6/102 (5.88%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

18/102 (17.65%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

28/102 (27.45%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

6/102 (5.88%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

49/102 (48.04%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

8/102 (7.84%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

13/102 (12.75%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

19/102 (18.63%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

31/102 (30.39%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

7/102 (6.86%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

9/102 (8.82%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

6/102 (5.88%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

11/102 (10.78%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

13/102 (12.75%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 25.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
Redacted CSR synopsis
Download
Redacted SAP
Download
Redacted CSP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted CSR synopsis

Redacted SAP

Redacted CSP

Trial Results Summaries