Trial Outcomes & Findings for 4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer (NCT NCT03364348)
NCT ID: NCT03364348
Last Updated: 2022-10-19
Results Overview
Dose-limiting toxicities (DLTs) within the first 2 cycles (6 weeks) of treatment were assessed. DLTs are treatment-related adverse events defined as: * Neutropenia Grade (Gr) 4 \>7 days * Febrile neutropenia, defined as absolute neutrophil count \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for \>1 hour * Neutropenic infection ≥Gr 3 * Thrombocytopenia ≥Gr 4, or with bleeding Gr 3 * Non-laboratory toxicities ≥Gr 3, except nausea, vomiting, or diarrhea recovering to \<Gr 2 within 48 hours. * Laboratory abnormalities \[other than aspartate aminotransferase / alanine aminotransferase (AST/ALT)\] ≥Gr 3, if: * Medical intervention required * Hospitalization required, or * \>24 hours * AST \& ALT Gr 4, or \>3×ULN * Total bilirubin \>2×ULN, with no elevation of alkaline phosphatase The outcome is reported as the number of DLTs observed per group, a number with dispersion.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
6 weeks
Results posted on
2022-10-19
Participant Flow
Participant milestones
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
2
|
3
|
10
|
|
Overall Study
COMPLETED
|
3
|
2
|
3
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer
Baseline characteristics by cohort
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
10 participants
n=4 Participants
|
18 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 6 weeksDose-limiting toxicities (DLTs) within the first 2 cycles (6 weeks) of treatment were assessed. DLTs are treatment-related adverse events defined as: * Neutropenia Grade (Gr) 4 \>7 days * Febrile neutropenia, defined as absolute neutrophil count \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for \>1 hour * Neutropenic infection ≥Gr 3 * Thrombocytopenia ≥Gr 4, or with bleeding Gr 3 * Non-laboratory toxicities ≥Gr 3, except nausea, vomiting, or diarrhea recovering to \<Gr 2 within 48 hours. * Laboratory abnormalities \[other than aspartate aminotransferase / alanine aminotransferase (AST/ALT)\] ≥Gr 3, if: * Medical intervention required * Hospitalization required, or * \>24 hours * AST \& ALT Gr 4, or \>3×ULN * Total bilirubin \>2×ULN, with no elevation of alkaline phosphatase The outcome is reported as the number of DLTs observed per group, a number with dispersion.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Dose-limiting Toxicities (DLTs)
|
0 Dose-limiting toxicities (DLTs)
|
0 Dose-limiting toxicities (DLTs)
|
0 Dose-limiting toxicities (DLTs)
|
0 Dose-limiting toxicities (DLTs)
|
SECONDARY outcome
Timeframe: 3 monthsObjective tumor response (ORR) per RECIST v1.1 was assessed after 4 cycles (3 months) of treatment. RECIST v1.1 was assessed on target lesions as: * Complete Response (CR): Complete disappearance of all lesions with the exception of nodal disease. All target lymph nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of all measurable lesions. * Progressive Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of measurable lesions. * Stable Disease (SD): All lesions assessed, but not CR, PR, or PD. Per protocol, the outcome is reported for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) as the number of participants with the indicated clinical response, a number without dispersion.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=10 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Objective Tumor Response (ORR)
Complete Response (CR)
|
0 participants
|
—
|
—
|
—
|
|
Objective Tumor Response (ORR)
Partial Response (PR)
|
1 participants
|
—
|
—
|
—
|
|
Objective Tumor Response (ORR)
Progressive Disease (PD)
|
5 participants
|
—
|
—
|
—
|
|
Objective Tumor Response (ORR)
Stable Disease (SD)
|
4 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Not all participants in Cohort 2B achieved a clinical response within 4 cycles (3 months).
Time-to-tumor response (TTR) was assessed per RECIST v1.1, in participants who have at least 1 on-study tumor assessment \& respond within 4 cycles (3 months). RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. By definition, TTR an assessment of the tumor response, meaning a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 4 cycles (3 months).
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=1 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Time-to-tumor Response (TTR)
|
12 weeks
Interval 12.0 to 12.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 260 weeksPopulation: This analysis includes only those Cohort 2B participants who had a Complete Response (CR) or a Partial Response (PR).
Duration of response (DoR) was assessed in participants who have 1+ on-study tumor assessment(s) and have a clinical response, through up to 5 years after treatment. RECIST v1.1 was assessed as: * Complete Response (CR): Complete disappearance of target lesions with the exception of nodal disease. Target nodes must decrease to normal size (short axis \< 10 mm). * Partial Response (PR): ≥ 30% decrease in the sum of diameters of target measurable lesions. * Progression Disease (PD): Increase in lesion size ≥ 5 mm and ≥ 20% increase in the sum of diameters of target measurable lesions. * Stable Disease (SD): Target lesions assessed, but not CR, PR, or PD. By definition, DoR is an assessment of tumor response, meaning the participants achieved a CR or a PR. Per protocol, the outcome is reported as the median with full range for participants in Cohort 2B (ado-trastuzumab emtansine + utomilumab) achieving a clinical response within 5 years (260 weeks).
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Duration of Response (DoR)
|
54 weeks
Interval 45.0 to 63.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 128 weeksProgression-free survival (PFS) means the participants remained alive without disease progression (DP). DP was defined per RECIST v1.1 as an increase in lesion size ≥ 5 mm or ≥ 20% increase in the sum of diameters of target measurable lesions. The outcome is reported as the median time that participants survived without DP, with full range.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Progression-free Survival (PFS)
|
9 weeks
Interval 6.0 to 15.0
|
15 weeks
Interval 12.0 to 17.0
|
45 weeks
Interval 12.0 to 128.0
|
12 weeks
Interval 3.0 to 85.0
|
SECONDARY outcome
Timeframe: Up to 128 weeksAdverse events while receiving treatment and within 30 days were assessed by treatment group for severity (as graded by NCI CTCAE v5). The outcome is reported by treatment group as the numbers of adverse events by treatment group, numbers without dispersion.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Adverse Events by Severity Grade 1 to 5
CTCAE Grade 1
|
4 adverse events
|
10 adverse events
|
71 adverse events
|
121 adverse events
|
|
Adverse Events by Severity Grade 1 to 5
CTCAE Grade 2
|
11 adverse events
|
4 adverse events
|
17 adverse events
|
39 adverse events
|
|
Adverse Events by Severity Grade 1 to 5
CTCAE Grade 3
|
5 adverse events
|
0 adverse events
|
3 adverse events
|
9 adverse events
|
|
Adverse Events by Severity Grade 1 to 5
CTCAE Grade 4
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
|
Adverse Events by Severity Grade 1 to 5
CTCAE Grade 5
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
SECONDARY outcome
Timeframe: Up to 128 weeksAdverse events while receiving treatment and within 30 days were assessed by treatment group for relationship to the study treatments. The outcome is reported as the numbers of related adverse events by treatment group, numbers without dispersion.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Adverse Event Relationship to Study Drugs
Not related
|
3 adverse events
|
2 adverse events
|
14 adverse events
|
24 adverse events
|
|
Adverse Event Relationship to Study Drugs
Unlikely related
|
15 adverse events
|
8 adverse events
|
15 adverse events
|
29 adverse events
|
|
Adverse Event Relationship to Study Drugs
Possibly related
|
1 adverse events
|
4 adverse events
|
46 adverse events
|
70 adverse events
|
|
Adverse Event Relationship to Study Drugs
Probably related
|
1 adverse events
|
0 adverse events
|
11 adverse events
|
49 adverse events
|
|
Adverse Event Relationship to Study Drugs
Definitely related
|
0 adverse events
|
0 adverse events
|
5 adverse events
|
0 adverse events
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 128 weeksAdverse events that were laboratory value abnormalities that occurred during treatment or within 30 days, were assessed by treatment group. The outcome is reported as the number of laboratory abnormalities by treatment group that were laboratory value abnormalities (Yes) or not (No), numbers without dispersion.
Outcome measures
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 Participants
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 Participants
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 Participants
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Laboratory Value Abnormalities
Yes
|
1 adverse events
|
2 adverse events
|
18 adverse events
|
18 adverse events
|
|
Laboratory Value Abnormalities
no
|
18 adverse events
|
12 adverse events
|
73 adverse events
|
152 adverse events
|
Adverse Events
Cohort 1A (Trastuzumab + Utomilumab)
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 1B (Trastuzumab + Utomilumab)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 participants at risk
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 participants at risk
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 participants at risk
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 participants at risk
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural hemorrhage
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
Other adverse events
| Measure |
Cohort 1A (Trastuzumab + Utomilumab)
n=3 participants at risk
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
|
Cohort 1B (Trastuzumab + Utomilumab)
n=2 participants at risk
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
|
Cohort 2A (Ado-trastuzumab Emtansine + Utomilumab)
n=3 participants at risk
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
Cohort 2B (Ado-trastuzumab Emtansine + Utomilumab)
n=10 participants at risk
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
100.0%
2/2 • Number of events 2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
40.0%
4/10 • Number of events 7 • 128 weeks
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
General disorders
Chills
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
40.0%
4/10 • Number of events 4 • 128 weeks
|
|
General disorders
Edema limbs
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
100.0%
3/3 • Number of events 10 • 128 weeks
|
60.0%
6/10 • Number of events 9 • 128 weeks
|
|
General disorders
Fever
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 9 • 128 weeks
|
40.0%
4/10 • Number of events 5 • 128 weeks
|
|
General disorders
Flu-like symptoms
|
0.00%
0/3 • 128 weeks
|
100.0%
2/2 • Number of events 2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
General disorders
General disorders and administration site conditions - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
General disorders
Pain
|
66.7%
2/3 • Number of events 3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
30.0%
3/10 • Number of events 4 • 128 weeks
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Infections and infestations
Infections and infestations - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Infections and infestations
Laryngitis
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Infections and infestations
Paronychia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Infections and infestations
Urinary tract infection
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
50.0%
5/10 • Number of events 10 • 128 weeks
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
30.0%
3/10 • Number of events 3 • 128 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
66.7%
2/3 • Number of events 2 • 128 weeks
|
70.0%
7/10 • Number of events 11 • 128 weeks
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
50.0%
5/10 • Number of events 10 • 128 weeks
|
|
Investigations
White blood cell decreased
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
66.7%
2/3 • Number of events 3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 5 • 128 weeks
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
20.0%
2/10 • Number of events 3 • 128 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 3 • 128 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Nervous system disorders
Amnesia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • 128 weeks
|
50.0%
1/2 • Number of events 2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
40.0%
4/10 • Number of events 7 • 128 weeks
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 4 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Psychiatric disorders
Hallucinations
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Reproductive system and breast disorders
Vaginal dryness
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
66.7%
2/3 • Number of events 3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • Number of events 4 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
66.7%
2/3 • Number of events 5 • 128 weeks
|
40.0%
4/10 • Number of events 6 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 3 • 128 weeks
|
30.0%
3/10 • Number of events 3 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/3 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
10.0%
1/10 • Number of events 2 • 128 weeks
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Surgical and medical procedures
Surgical and medical procedures - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Vascular disorders
Lymphedema
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 3 • 128 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 7 • 128 weeks
|
50.0%
5/10 • Number of events 15 • 128 weeks
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Cardiac disorders
Cardiac disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Cardiac disorders
Chest pain - cardiac
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Eye disorders
Dry eye
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Eye disorders
Eye disorders - Other
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
0.00%
0/10 • 128 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
33.3%
1/3 • Number of events 1 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3 • Number of events 2 • 128 weeks
|
50.0%
1/2 • Number of events 1 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 3 • 128 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 2 • 128 weeks
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
20.0%
2/10 • Number of events 3 • 128 weeks
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/3 • 128 weeks
|
0.00%
0/2 • 128 weeks
|
0.00%
0/3 • 128 weeks
|
10.0%
1/10 • Number of events 1 • 128 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place