Metastatic Breast Cancer
Conditions
Keywords
Oncology, HER3, Antibody drug conjugate, Developmental Phase I/II
Brief summary
This is an open-label, three-part, multiple-dose study to evaluate safety, tolerability, and efficacy of U3-1402 in patients with HER3-positive metastatic breast cancer. HER3 is a unique member of the human epidermal growth factor receptor, which defines a certain type of cancer. The number of patients and treatment cycles are not fixed in this study. Subjects who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, progressive disease (PD), unacceptable toxicity, or death may continue the study treatment until the end of the trial.
Interventions
U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)
Sponsors
Daiichi Sankyo
Merck Sharp & Dohme LLC
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Is 18 Years and older in the United States or 20 Years and older in Japan 2. Has a pathologically documented advanced/unresectable or metastatic breast cancer 3. Documented HER3-positive disease measured by immunohistochemistry (IHC) 4. Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available 5. Has an Eastern Cooperative Oncology Group Performance Status 0-1 6. Has Left Ventricular Ejection Fraction ≥ 50% 7. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part: 8. Has received 2-6 prior chemotherapy regimens for breast cancer, at least 2 of which were administered for treatment of advanced/unresectable or metastatic disease. At least 1 prior chemotherapeutic regimen must have included a taxane, administered in the neoadjuvant, adjuvant, or advanced setting. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.) Additional Inclusion Criteria for Dose Expansion Part Only: 9. Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression 10. Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.) Additional Inclusion Criteria for Dose Expansion Part TNBC cohort Only: 11. Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines 12. Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer. Key
Exclusion criteria
1. Prior treatment with a HER3 antibody 2. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201) 3. Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment 4. Has a medical history of myocardial infarction or unstable angina 5. Has a corrected QT prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females 6. Has a medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period 7. Has clinically significant corneal disease Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Baseline up to 28 days post last dose, up to approximately 9 months | AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose |
| Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | From screening until disease progresses, up to approximately 9 months | CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Expansion Part: AUC of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
| Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Finding Part: Cmax of Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Finding Part: Tmax of Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Expansion Part: Tmax in Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay. |
| Dose Finding Part: AUC of Anti-HER3-ac-DXd | Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days) | The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay. |
Countries
Japan, United States
Participant flow
Recruitment details
A total of 182 participants who met all inclusion criteria and no exclusion criteria received at least 1 dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: Cohort 1.6 mg/kg Participants with HER3-positive metastatic breast cancer who received U3-1402 1.6 mg/kg administered via intravenous (IV) solution at 3-week intervals. | 3 |
| Dose Escalation: Cohort 3.2 mg/kg Participants with HER3-positive metastatic breast cancer who received U3-1402 3.2 mg/kg administered via intravenous (IV) solution at 3-week intervals. | 3 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg Participants with HER3-positive metastatic breast cancer who received U3-1402 4.8 mg/kg administered via intravenous (IV) solution at 3-week intervals. | 15 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg Participants with HER3-positive metastatic breast cancer who received U3-1402 6.4 mg/kg administered via intravenous (IV) solution at 3-week intervals. | 15 |
| Dose Escalation: Cohort 8.0 mg/kg Participants with HER3-positive metastatic breast cancer who received U3-1402 8.0 mg/kg administered via intravenous (IV) solution at 3-week intervals. | 6 |
| Dose Finding: 3.2/4.8/6.4 mg/kg Participants who received U3-1402 (Cycle 1: 3.2 mg/kg IV infusion Q3W; Cycle 2: 4.8 mg/kg IV infusion Q3W; Cycle 3 and all subsequent cycles: 6.4 mg/kg IV infusion Q3W). | 12 |
| Dose Finding: 4.2/6.4 mg/kg Participants who received U3-1402 (Cycles 1-3: 4.2 mg/kg IV infusion Q3W; Subsequent cycles: 6.4 mg/kg IV infusion Q3W). | 12 |
| Dose Expansion: HER3 High 4.8 mg/kg Participants with HER3-high, HER2-negative, HR-positive breast cancer who received 4.8 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals. | 33 |
| Dose Expansion: HER3-High 6.4 mg/kg Participants with HER3-high, HER2-negative, HR-positive breast cancer who received 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals. | 31 |
| Dose Expansion: HER3-Low 6.4 mg/kg Participants with HER3-low, HER2-negative, HR-positive breast cancer who received 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals. | 21 |
| Dose Expansion: TNBC 6.4 mg/kg Participants with HER3-High, triple negative breast cancer who received 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals. | 31 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation | Adverse Event | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Clinical progression | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Due to investigator's decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Due to side effect management of chemotherapy | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Progressive disease per RECIST v1.1 | 3 | 3 | 11 | 10 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Expansion | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 3 |
| Dose Expansion | Clinical progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 1 | 4 |
| Dose Expansion | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
| Dose Expansion | Due to investigator's decision because patient was a candidate for surgery | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dose Expansion | Due to investigator's decision considering patient's liver condition | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Expansion | Due to investigator's decision due to patient's general condition | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Dose Expansion | Patient withdrew consent following 50 treatment cycles | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion | Progressive disease per RECIST v1.1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 23 | 24 | 17 | 23 |
| Dose Expansion | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Dose Finding | Adverse Event | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Dose Finding | Progressive disease per RECIST v1.1 | 0 | 0 | 0 | 0 | 0 | 8 | 11 | 0 | 0 | 0 | 0 |
| Dose Finding | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation: Cohort 8.0 mg/kg | Dose Finding: 3.2/4.8/6.4 mg/kg | Dose Finding: 4.2/6.4 mg/kg | Dose Expansion: HER3 High 4.8 mg/kg | Dose Expansion: HER3-High 6.4 mg/kg | Dose Expansion: HER3-Low 6.4 mg/kg | Dose Expansion: TNBC 6.4 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 10.41 | 62.3 years STANDARD_DEVIATION 22.74 | 52.1 years STANDARD_DEVIATION 13.38 | 58.7 years STANDARD_DEVIATION 11.76 | 50.2 years STANDARD_DEVIATION 8.45 | 51.8 years STANDARD_DEVIATION 13.79 | 50.7 years STANDARD_DEVIATION 11.92 | 56.0 years STANDARD_DEVIATION 11.95 | 56.9 years STANDARD_DEVIATION 11.04 | 55.4 years STANDARD_DEVIATION 12.92 | 58.0 years STANDARD_DEVIATION 13.73 | 55.6 years STANDARD_DEVIATION 12.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 3 Participants | 15 Participants | 15 Participants | 6 Participants | 12 Participants | 12 Participants | 19 Participants | 18 Participants | 15 Participants | 24 Participants | 142 Participants |
| Race/Ethnicity, Customized Black of African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 11 Participants | 6 Participants | 6 Participants | 34 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 15 Participants | 15 Participants | 6 Participants | 12 Participants | 12 Participants | 33 Participants | 31 Participants | 21 Participants | 31 Participants | 182 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 | 13 / 15 | 11 / 15 | 2 / 6 | 10 / 12 | 10 / 12 | 22 / 33 | 24 / 31 | 18 / 21 | 16 / 31 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 15 / 15 | 15 / 15 | 6 / 6 | 12 / 12 | 12 / 12 | 32 / 33 | 31 / 31 | 21 / 21 | 31 / 31 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 3 / 15 | 9 / 15 | 2 / 6 | 4 / 12 | 3 / 12 | 10 / 33 | 12 / 31 | 7 / 21 | 8 / 31 |
Outcome results
Primary
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose
Time frame: Baseline up to 28 days post last dose, up to approximately 9 months
Population: Adverse events are reported from the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 2 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 3 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 1 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 3 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 1 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 2 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 1 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 15 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 7 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 2 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 11 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 3 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 13 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 2 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 15 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 12 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 2 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 6 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 5 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 5 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 3 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 8 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 12 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 7 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 3 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 2 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 0 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 12 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 0 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 0 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 4 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 6 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 4 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 4 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 1 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 32 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 16 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 20 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 2 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 2 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 24 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 15 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 31 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 9 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 21 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 1 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 2 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 16 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 3 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 10 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose reduction | 8 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 31 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with death | 1 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE Grade ≥3 | 27 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with study treatment discontinuation | 3 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) | Any TEAE associated with dose interruption | 20 Participants |
Primary
Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response.
Time frame: From screening until disease progresses, up to approximately 9 months
Population: Best overall tumor response was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 2 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 1 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 0 Participants |
| Dose Escalation: Cohort 1.6 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 1 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 2 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Escalation: Cohort 3.2 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 1 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 3 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 7 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 5 Participants |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 5 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 7 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 8 Participants |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 7 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 1 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 3 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 3 Participants |
| Dose Escalation: Cohort 8.0 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 2 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 2 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 5 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 0 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 5 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Finding: 3.2/4.8/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 5 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 3 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 6 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 1 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 3 Participants |
| Dose Finding: 4.2/6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 2 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 11 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 1 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 11 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 2 Participants |
| Dose Expansion: HER3 High 4.8 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 19 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 7 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 2 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 17 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 5 Participants |
| Dose Expansion: HER3-High 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 5 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 7 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 7 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 7 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 3 Participants |
| Dose Expansion: HER3-Low 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 4 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Objective response rate (ORR) | 5 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 0 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Nonevaluable (NE) | 2 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Partial response (PR) | 5 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Stable disease (SD)/Non-CR/Non-PD | 21 Participants |
| Dose Expansion: TNBC 6.4 mg/kg | Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 3 Participants |
Secondary
Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 111 ug*d/mL | — |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 1 | 114 ug*d/mL | Standard Deviation 14.7 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 115 ug*d/mL | Standard Deviation 14.3 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 3 | 111 ug*d/mL | — |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 114 ug*d/mL | Standard Deviation 14.5 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 311 ug*d/mL | Standard Deviation 122 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 219 ug*d/mL | Standard Deviation 61 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 3 | 312 ug*d/mL | Standard Deviation 124 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 226 ug*d/mL | Standard Deviation 67.3 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 1 | 219 ug*d/mL | Standard Deviation 61 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 408 ug*d/mL | Standard Deviation 115 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 1 | 416 ug*d/mL | Standard Deviation 128 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 3 | 700 ug*d/mL | Standard Deviation 234 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 682 ug*d/mL | Standard Deviation 194 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 447 ug*d/mL | Standard Deviation 153 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 729 ug*d/mL | Standard Deviation 186 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 1 | 635 ug*d/mL | Standard Deviation 171 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 1050 ug*d/mL | Standard Deviation 249 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 671 ug*d/mL | Standard Deviation 169 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 3 | 1080 ug*d/mL | Standard Deviation 280 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 848 ug*d/mL | Standard Deviation 248 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 1200 ug*d/mL | Standard Deviation 450 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 1 | 847 ug*d/mL | Standard Deviation 248 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 839 ug*d/mL | Standard Deviation 203 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody | AUClast, Cycle 3 | 1570 ug*d/mL | — |
Secondary
Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 2420 ng*d/mL | — |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 2470 ng*d/mL | Standard Deviation 435 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 2490 ng*d/mL | Standard Deviation 440 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 2400 ng*d/mL | — |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 2470 ng*d/mL | Standard Deviation 438 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 5900 ng*d/mL | Standard Deviation 2050 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 4420 ng*d/mL | Standard Deviation 1020 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 5920 ng*d/mL | Standard Deviation 1070 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 4470 ng*d/mL | Standard Deviation 1060 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 4420 ng*d/mL | Standard Deviation 1020 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 8600 ng*d/mL | Standard Deviation 1870 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 8690 ng*d/mL | Standard Deviation 1070 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 13800 ng*d/mL | Standard Deviation 3730 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 13700 ng*d/mL | Standard Deviation 3700 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 8990 ng*d/mL | Standard Deviation 2230 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 14600 ng*d/mL | Standard Deviation 3510 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 13000 ng*d/mL | Standard Deviation 3310 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 20300 ng*d/mL | Standard Deviation 3200 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 13600 ng*d/mL | Standard Deviation 3020 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 20500 ng*d/mL | Standard Deviation 4070 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 16700 ng*d/mL | Standard Deviation 4170 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 21000 ng*d/mL | Standard Deviation 5420 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 16700 ng*d/mL | Standard Deviation 4170 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 18300 ng*d/mL | Standard Deviation 4920 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 27100 ng*d/mL | — |
Secondary
Dose Escalation Part: Cmax of Total Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 1 | 39.8 ug/mL | Standard Deviation 9.55 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 3 | 37.6 ug/mL | — |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 1 | 61.6 ug/mL | Standard Deviation 8.41 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 3 | 66.8 ug/mL | Standard Deviation 11.2 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 1 | 95.8 ug/mL | Standard Deviation 13.5 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 3 | 112 ug/mL | Standard Deviation 14.1 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 3 | 149 ug/mL | Standard Deviation 24.7 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 1 | 136 ug/mL | Standard Deviation 26.8 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 1 | 149 ug/mL | Standard Deviation 35.3 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Cmax of Total Anti-HER3 Antibody | Cmax, Cycle 3 | 165 ug/mL | Standard Deviation 25.4 |
Secondary
Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed using the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 1040 ng/mL | Standard Deviation 217 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 948 ng/mL | — |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 1740 ng/mL | Standard Deviation 421 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 1820 ng/mL | Standard Deviation 284 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 2950 ng/mL | Standard Deviation 661 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 3020 ng/mL | Standard Deviation 572 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 3870 ng/mL | Standard Deviation 488 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 3660 ng/mL | Standard Deviation 1080 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 4210 ng/mL | Standard Deviation 568 |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 3720 ng/mL | Standard Deviation 973 |
Secondary
Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.85 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 2.18 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.68 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 1.83 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.83 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 1.88 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 2.03 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 2.05 hours |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.98 hours |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 4.22 hours |
Secondary
Dose Escalation Part: Tmax of Total Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 1 | 1.85 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 3 | 2.18 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 1 | 1.68 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 3 | 1.83 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 1 | 1.95 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 3 | 1.88 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 3 | 2.02 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 1 | 2.00 hours |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 1 | 2.14 hours |
| Dose Escalation: Cohort 8.0 mg/kg | Dose Escalation Part: Tmax of Total Anti-HER3 Antibody | Tmax, Cycle 3 | 2.07 hours |
Secondary
Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 525 ug*d/mL | Standard Deviation 174 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 831 ug*d/mL | Standard Deviation 391 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 483 ug*d/mL | Standard Deviation 140 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 874 ug*d/mL | Standard Deviation 365 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 1070 ug*d/mL | Standard Deviation 656 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 564 ug*d/mL | Standard Deviation 178 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 1200 ug*d/mL | Standard Deviation 536 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 570 ug*d/mL | Standard Deviation 248 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 580 ug*d/mL | Standard Deviation 200 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 1070 ug*d/mL | Standard Deviation 381 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 1030 ug*d/mL | Standard Deviation 366 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 543 ug*d/mL | Standard Deviation 225 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 940 ug*d/mL | Standard Deviation 243 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 1000 ug*d/mL | Standard Deviation 266 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 528 ug*d/mL | Standard Deviation 166 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 542 ug*d/mL | Standard Deviation 158 |
Secondary
Dose Expansion Part: AUC of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 10500 ng*d/mL | Standard Deviation 2850 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 14200 ng*d/mL | Standard Deviation 6540 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 10100 ng*d/mL | Standard Deviation 2480 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 15600 ng*d/mL | Standard Deviation 6850 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 20000 ng*d/mL | Standard Deviation 14400 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 11900 ng*d/mL | Standard Deviation 3400 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 22400 ng*d/mL | Standard Deviation 12700 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 11500 ng*d/mL | Standard Deviation 3930 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 11700 ng*d/mL | Standard Deviation 4430 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 19300 ng*d/mL | Standard Deviation 6830 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 20300 ng*d/mL | Standard Deviation 6830 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 11100 ng*d/mL | Standard Deviation 4840 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 19800 ng*d/mL | Standard Deviation 5540 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 20400 ng*d/mL | Standard Deviation 6230 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 11400 ng*d/mL | Standard Deviation 3820 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 11700 ng*d/mL | Standard Deviation 3380 |
Secondary
Dose Expansion Part: Cmax in Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 1 | 107 ug/mL | Standard Deviation 20.3 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 3 | 121 ug/mL | Standard Deviation 27.7 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 3 | 152 ug/mL | Standard Deviation 25.8 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 1 | 129 ug/mL | Standard Deviation 21.2 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 1 | 126 ug/mL | Standard Deviation 28.4 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 3 | 140 ug/mL | Standard Deviation 29.7 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 1 | 127 ug/mL | Standard Deviation 24.4 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Cmax in Anti-HER3 Antibody | Cmax, Cycle 3 | 146 ug/mL | Standard Deviation 21.7 |
Secondary
Dose Expansion Part: Cmax of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 3010 ng/mL | Standard Deviation 631 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 3020 ng/mL | Standard Deviation 606 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 4000 ng/mL | Standard Deviation 672 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 3520 ng/mL | Standard Deviation 619 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 3630 ng/mL | Standard Deviation 744 |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 4150 ng/mL | Standard Deviation 892 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 3610 ng/mL | Standard Deviation 878 |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 4090 ng/mL | Standard Deviation 506 |
Secondary
Dose Expansion Part: Tmax in Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were assessed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 1 | 1.92 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 3 | 1.95 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 3 | 2.10 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 1 | 2.00 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 1 | 1.87 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 3 | 1.98 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 1 | 1.93 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Tmax in Anti-HER3 Antibody | Tmax, Cycle 3 | 2.00 hours |
Secondary
Dose Expansion Part: Tmax of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.90 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 1.78 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 0.93 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.97 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.98 hours |
| Dose Escalation/Dose Finding: Cohort 4.8 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 2.02 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.95 hours |
| Dose Escalation/Dose Finding: Cohort 6.4 mg/kg | Dose Expansion Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 2.03 hours |
Secondary
Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 839 ug*d/mL | Standard Deviation 220 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 253 ug*d/mL | Standard Deviation 58 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 933 ug*d/mL | Standard Deviation 174 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 260 ug*d/mL | Standard Deviation 63.4 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 235 ug*d/mL | Standard Deviation 92.7 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 3 | 616 ug*d/mL | Standard Deviation 138 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 4 | 1090 ug*d/mL | Standard Deviation 276 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCinf, Cycle 1 | 335 ug*d/mL | Standard Deviation 102 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 1 | 302 ug*d/mL | Standard Deviation 87.4 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 3 | 486 ug*d/mL | Standard Deviation 199 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUClast, Cycle 4 | 1110 ug*d/mL | Standard Deviation 280 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody | AUCtau, Cycle 1 | 341 ug*d/mL | Standard Deviation 103 |
Secondary
Dose Finding Part: AUC of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 16600 ng*d/mL | Standard Deviation 3760 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 6160 ng*d/mL | Standard Deviation 1160 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 18300 ng*d/mL | Standard Deviation 2740 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 6220 ng*d/mL | Standard Deviation 1200 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 5540 ng*d/mL | Standard Deviation 2020 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 3 | 11600 ng*d/mL | Standard Deviation 1880 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 4 | 22300 ng*d/mL | Standard Deviation 8010 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCinf, Cycle 1 | 7800 ng*d/mL | Standard Deviation 1990 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 1 | 7160 ng*d/mL | Standard Deviation 1900 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 3 | 9360 ng*d/mL | Standard Deviation 3670 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUClast, Cycle 4 | 23100 ng*d/mL | Standard Deviation 8130 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: AUC of Anti-HER3-ac-DXd | AUCtau, Cycle 1 | 7630 ng*d/mL | Standard Deviation 1920 |
Secondary
Dose Finding Part: Cmax of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 1980 ng/mL | Standard Deviation 300 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 4230 ng/mL | Standard Deviation 1120 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 1 | 2370 ng/mL | Standard Deviation 566 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 3 | 2830 ng/mL | Standard Deviation 760 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3-ac-DXd | Cmax, Cycle 4 | 4310 ng/mL | Standard Deviation 1120 |
Secondary
Dose Finding Part: Cmax of Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Cmax of Anti-HER3 Antibody | Cmax, Cycle 1 | 67.9 ug/mL | Standard Deviation 11.3 |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Cmax of Anti-HER3 Antibody | Cmax, Cycle 3 | 139 ug/mL | Standard Deviation 25 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3 Antibody | Cmax, Cycle 1 | 87.2 ug/mL | Standard Deviation 33.2 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3 Antibody | Cmax, Cycle 3 | 94.9 ug/mL | Standard Deviation 10.6 |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Cmax of Anti-HER3 Antibody | Cmax, Cycle 4 | 145 ug/mL | Standard Deviation 16.6 |
Secondary
Dose Finding Part: Tmax of Anti-HER3-ac-DXd
The serum concentrations for anti-HER3-ac-DXd were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 1.86 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 2.00 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 1 | 2.01 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 3 | 1.93 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3-ac-DXd | Tmax, Cycle 4 | 1.83 hours |
Secondary
Dose Finding Part: Tmax of Anti-HER3 Antibody
The serum concentrations for total anti-HER3 antibody LC/MS were quantified using the IC-LC/MS assay.
Time frame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
Population: Pharmacokinetic data were analyzed in participants with available data in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Tmax of Anti-HER3 Antibody | Tmax, Cycle 1 | 1.85 hours |
| Dose Escalation: Cohort 1.6 mg/kg | Dose Finding Part: Tmax of Anti-HER3 Antibody | Tmax, Cycle 3 | 3.80 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3 Antibody | Tmax, Cycle 1 | 1.80 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3 Antibody | Tmax, Cycle 3 | 1.93 hours |
| Dose Escalation: Cohort 3.2 mg/kg | Dose Finding Part: Tmax of Anti-HER3 Antibody | Tmax, Cycle 4 | 3.80 hours |