Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast
Conditions
Keywords
HER2, T-DXd, DS-8201a, Trastuzumab Deruxtecan, Metastatic, Solid Tumors, Histology Agnostic
Brief summary
This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.
Interventions
DRUGTrastuzumab deruxtecan
Trastuzumab deruxtecan (T-DXd) by intravenous infusion
Sponsors
AstraZeneca
Daiichi Sankyo Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (open-label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Adults ≥18 years old. Other age restrictions may apply as per local regulations. * Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772\_A775dup / A775\_G776insYVMA, L755S, G778\_P780dup / P780\_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options. * Prior HER2 targeted therapy is permitted. * All patients must provide an FFPE tumor sample for retrospective central HER2 testing. * LVEF ≥50% * ECOG 0-1 * All patients have measurable target disease assessed by the Investigator based on RECIST v1.1
Exclusion criteria
* HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. * HER2 mutant NSCLC. * Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke. * History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening * Corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG. * Lung-specific intercurrent clinically significant severe illnesses. * History of active primary immunodeficiency, known HIV, active HBV or HCV infection * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals * Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). * Has spinal cord compression or clinically active central nervous system metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment | 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) | 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. |
| Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | 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) | 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. |
| PFS as Per RECIST v1.1 Using ICR and Investigator Assessment | 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) | 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. |
| Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | At Months 6 and 12 | 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. |
| Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment | 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) | 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. |
| Overall Survival (OS) | From the date of first treatment administration up to death, approximately 24 months | 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. |
| Percentage of Participants Alive at 6 and 12 Months | At Months 6 and 12 | 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. |
| Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | 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) | Serum samples were collected at specified timepoints to determine serum concentrations of T-DXd and total anti-HER2 antibody. |
| Serum Concentrations of Deruxtecan (MAAA-1181a) | 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) | Serum samples were collected at specified timepoints to determine serum concentrations of MAAA-1181a. |
| Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Up to approximately 24 months | 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. |
Countries
Belgium, Canada, Denmark, France, Italy, Japan, South Korea, Spain, United States
Participant flow
Recruitment details
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
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 102 |
| Total | 102 |
Baseline characteristics
| Characteristic | T-DXd |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 10.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 38 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 58 / 102 |
| other Total, other adverse events | 96 / 102 |
| serious Total, serious adverse events | 36 / 102 |
Outcome results
Primary
Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)
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)
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T-DXd | Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR) | 29.4 percentage of participants |
Secondary
Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment
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)
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T-DXd | Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment | 32.4 percentage of participants |
Secondary
Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DCR at 6 weeks by ICR | 75.5 percentage of participants |
| T-DXd | Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DCR at 6 weeks by Investigator assessment | 70.6 percentage of participants |
| T-DXd | Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DCR at 12 weeks by ICR | 53.9 percentage of participants |
| T-DXd | Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DCR at 12 weeks by Investigator assessment | 55.9 percentage of participants |
Secondary
Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
Population: The FAS consisted of all participants who received at least 1 dose of study treatment. Participants with response were evaluated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DoR by ICR | NA months |
| T-DXd | Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DoR by Investigator assessment | 11.0 months |
Secondary
Overall Survival (OS)
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
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd | Overall Survival (OS) | 10.9 months |
Secondary
Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment
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
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS rate at 6 months by ICR | 41.4 percentage of participants |
| T-DXd | Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS rate at 6 months by Investigator assessment | 37.7 percentage of participants |
| T-DXd | Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS rate at 12 months by ICR | 30.9 percentage of participants |
| T-DXd | Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS rate at 12 months by Investigator assessment | 26.5 percentage of participants |
Secondary
Percentage of Participants Alive at 6 and 12 Months
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
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Percentage of Participants Alive at 6 and 12 Months | Survival rate at 6 months | 67.6 percentage of participants |
| T-DXd | Percentage of Participants Alive at 6 and 12 Months | Survival rate at 12 months | 46.3 percentage of participants |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | ADA positive at any visit (ADA prevalence) | 2.1 percentage of participants |
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | ADA incidence | 0 percentage of participants |
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Treatment-emergent ADA positive | 0 percentage of participants |
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Treatment-boosted ADA positive | 0 percentage of participants |
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Transiently positive ADA | 0 percentage of participants |
| T-DXd | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Persistently positive ADA | 0 percentage of participants |
Secondary
PFS as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
Population: The FAS consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | PFS as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS by ICR | 5.4 months |
| T-DXd | PFS as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS by Investigator assessment | 4.4 months |
Secondary
Serum Concentrations of Deruxtecan (MAAA-1181a)
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 2: Pre-infusion | 0.2 ng/mL | Standard Deviation 0.1 |
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 1: 15 minutes post-infusion | 4.7 ng/mL | Standard Deviation 2.9 |
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 1: 5 hours post-infusion | 10.5 ng/mL | Standard Deviation 5.1 |
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 4: 15 minutes post-infusion | 1.5 ng/mL | Standard Deviation 0.9 |
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 2: 15 minutes post-infusion | 2.2 ng/mL | Standard Deviation 1.5 |
| T-DXd | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 4: Pre-infusion | 0.3 ng/mL | Standard Deviation 0.2 |
| Unknown | Serum Concentrations of Deruxtecan (MAAA-1181a) | MAAA-1181a: Cycle 1: Pre-infusion | — ng/mL | — |
Secondary
Serum Concentrations of T-DXd and Total Anti-HER2 Antibody
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 1: 15 minutes post-infusion | 123.8 microgram/milliliter (mL) | Standard Deviation 52.8 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 1: 5 hours post-infusion | 122.1 microgram/milliliter (mL) | Standard Deviation 42.1 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 2: Pre-infusion | 6.2 microgram/milliliter (mL) | Standard Deviation 12.4 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 2: 15 minutes post-infusion | 144.4 microgram/milliliter (mL) | Standard Deviation 115.4 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 4: Pre-infusion | 9.9 microgram/milliliter (mL) | Standard Deviation 5.7 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 4: 15 minutes post-infusion | 122.1 microgram/milliliter (mL) | Standard Deviation 37.3 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 1: Pre-infusion | NA microgram/milliliter (mL) | — |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 1: 15 minutes post-infusion | 116.5 microgram/milliliter (mL) | Standard Deviation 50.8 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 1: 5 hours post-infusion | 115.4 microgram/milliliter (mL) | Standard Deviation 30.5 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 2: Pre-infusion | 11.2 microgram/milliliter (mL) | Standard Deviation 74.1 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 2: 15 minutes post-infusion | 132.2 microgram/milliliter (mL) | Standard Deviation 101.5 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 4: Pre-infusion | 7.7 microgram/milliliter (mL) | Standard Deviation 9.1 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | T-DXd: Cycle 4: 15 minutes post-infusion | 121.7 microgram/milliliter (mL) | Standard Deviation 40.1 |
| T-DXd | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Total anti-HER2 antibody: Cycle 1: Pre-infusion | NA microgram/milliliter (mL) | — |