HER2 Positive Breast CarcinomaPhase 1NCT03364348
4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer
A Phase 1 study testing Utomilumab, Trastuzumab and Ado-Trastuzumab Emtansine in people with HER2 Positive Breast Carcinoma and Recurrent Breast Carcinoma, run by George W. Sledge Jr. at 1 site in United States.
Trial summary
This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Positive Breast Carcinoma, Recurrent Breast Carcinoma, Stage III Breast Cancer
- What is being tested?
- Utomilumab, Trastuzumab and Ado-Trastuzumab Emtansine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2017to 14 Feb 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of biopsy proven HER2 overexpressing breast cancer and radiographic evidence of metastatic disease, or locally recurrent unresectable disease. The HER2 status can be determined either by immunohistochemistry (IHC) [IHC score, 3+] or by fluorescence in situ hybridization (FISH) [as defined by HER2/CEP 17 ratio ≥ 2.0, or HER2 copy number ≥ 6], or as otherwise defined by 2018 ASCO/CAP guidelines.
- Cohort 1 subjects must have received trastuzumab and a taxane separately or in combination (those who previously received ado-trastuzumab emtansine may accrue to Cohort 2).
- Subjects in Cohort 2 must have received at least 1 prior therapy including ado-trastuzumab emtansine.
- Subjects who discontinued prior trastuzumab or ado trastuzumab emtansine due to progressive or refractory disease are eligible for enrollment
- Available tumor samples. For eligibility, if no unstained slides remain, stained pathology slides may be reviewed at the treating institution. However, a tumor sample is required for research evaluations per the following (any of Item 1; 2; or 3, in order of preference).
- A FFPE tumor tissue block from a de novo fresh tumor biopsy obtained during screening will be requested, though not mandated.
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- A recently obtained archival FFPE tumor tissue block (or 10 to 15 unstained slides) from a primary or metastatic tumor resection or biopsy if the following criteria are met:
- The biopsy or resection was performed within 1 year of enrollment OR
- The subject has not received any intervening systemic anti cancer treatment from the time the tissue was obtained and enrolled onto the current study. OR
- Any archival FFPE tumor tissue block (or unstained slides) from primary tumor resection specimen (if not provided per above). The archival sample may have been collected at any time prior to the current study, regardless of any intervening therapy. If an FFPE tissue block cannot be provided, a minimum of 10 unstained slides (15 preferable) will be acceptable.
- Subjects must have evaluable OR measurable disease, as defined by RECIST v1.1.
- Performance status 0 to 1 (by Eastern Cooperative Oncology Group [ECOG] scale).
- Laboratory parameters (must satisfy all): Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (≥ 1500/µL) Platelet count ≥ 100 × 109/L (≥ 100,000 /µL) Hemoglobin ≥ 9.0 g/dL; subjects on therapeutic anticoagulation are eligible if there is no bleeding and they are on a stable dose of anticoagulation therapy (eg, on Coumadin with an INR of 2 to 3) for at least 7 days before registration (prior to the start of therapy, or stable heparin or Factor Xa inhibitor dose) Serum creatinine ≤ 1.5 × the ULN or calculated creatinine clearance (by Cockcroft Gault formula) ≥ 60 mL/min Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN Bilirubin ≤ 1.5 × ULN
- Subjects must not be pregnant or breastfeeding. A pregnancy test will be obtained if the subject is a woman of child bearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or and/or bilateral oophorectomy or who has not been naturally postmenopausal for at least 24 consecutive months (ie, who has had menses at any time in the preceding 24 consecutive months) with 2 pregnancy tests, one at screening, and another immediately preceding the initiation of treatment.
- Subjects must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment
- Left ventricular ejection fraction determined by echocardiogram or multiple gated acquisition scan (MUGA) (cardiac scan) must be 50% or higher.
Who cannot join
- Previously discontinued either trastuzumab or ado trastuzumab emtansine due to intolerance.
- Received any other investigational agents within 30 days of registration.
- Central nervous system (CNS) metastases, unless previously treated by either radiation therapy and/or surgical resection, clinically stable for at least 60 days and on a stable corticosteroid dose of ≤ 4 mg/day decadron (or equivalent steroid regimen) for at least 1 month. Subjects with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply:
- Therapy has been administered (surgery and/or radiation therapy);
- There is no additional treatment planned for brain metastases;
- The subject is clinically stable;
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- The subject is on a stable corticosteroid dose of ≤ 4 mg/day decadron (or equivalent steroid regimen) for at least 1 month.
- Prior malignancy (other than in situ cervical cancer, or basal cell or squamous cell carcinoma of the skin), unless treated with curative intent and without evidence of disease for 3 years or longer
- Administration of other prior anticancer therapies within 4 weeks of enrollment, except ongoing administration of a bisphosphonate drug or denosumab as treatment for bone metastasis
- Toxicities related to prior anticancer treatment (except alopecia) that have not resolved to ≤ Grade 1 according to common terminology criteria for adverse events (CTCAE v5) before registration or prior to start of therapy
- Currently receiving systemic antibiotic, antiviral, or antifungal therapy for the treatment of an active infection
- Systemic corticosteroid therapy at doses of greater than prednisone 5 mg daily (or dose-equivalent chronic steroid regimen) for therapeutic and not adrenal replacement indications (maintenance steroid use for adrenal insufficiency is permitted). Acute emergency administration, topical applications, inhaled sprays, eye drops or local injections of corticosteroids are allowed.
- History of bleeding diathesis
- Any co morbid medical condition deemed by the treating or principal investigator to possibly put the subject at significant risk for toxicity.
- Subject has known sensitivity to any of the products to be administered during dosing
- Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of venous thromboembolism within prior 6 months.
- Subject with reproductive potential who will not agree to use, during the study and for 60 days after the last dose of utomilumab or 6 months for ado trastuzumab emtansine or trastuzumab 2 highly effective method of contraceptive such as:
- Implants
- Injectables
- Intrauterine devices (IUDs) such as copper T or Levonorgestrel releasing intrauterine system (LNG IUS)
- Sexual abstinence
- Vasectomized partner
- Condom or occlusive cap (diaphragm or cervical/vault cap) supplemented with the use of a spermicide during treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: A Phase 1B Dose Escalation Trial of Human Anti 4 1BB Agonistic Antibody Utomilumab (PF 05082566) in Combination With Ado Trastuzumab Emtansine or Trastuzumab in Patients With HER2 Postive Advanced Breast Cancer
This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Monoclonal antibodies, such as utomilumab, trastuzumab emtansine, and trastuzumab may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVE:
Estimate the maximum tolerated dose (MTD) and determine the recommended dose (RP2D) of utomilumab in combination with ado-rastuzumab emtansine (T-DM1) or trastuzumab in subjects with HER2-positive advanced breast cancer.
SECONDARY OBJECTIVES:
- Determine the objective tumor response (ORR)
- Determine the time to tumor response (TTR)
- Determine the duration of response (DR)
- Determine progression free survival (PFS)
- Assess the safety and tolerability of utomilumab in combination with ado-trastuzumab emtansine or trastuzumab
OUTLINE: Patients are randomized to 1 of 2 cohorts.
COHORT 1: Dose 1: Utomilumab 20 mg IV + ado-trastuzumab emtansine (T-DM1) 3.6 mg/kg IV every 3 weeks. Dose 2: Dose Level 2 - Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks
COHORT 2: Dose 1: Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. Dose Level 2 - Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
- Conditions
- HER2 Positive Breast Carcinoma, Recurrent Breast Carcinoma, Stage III Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
- Being tested
- Utomilumab, Trastuzumab, Ado-Trastuzumab Emtansine
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UtomilumabDrug
Also called 4-1BB Agonist Monoclonal Antibody PF-05082566, PF-05082566, PF-2566
Given IV
TrastuzumabDrug
Also called ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2
Given IV
Ado-Trastuzumab EmtansineDrug
Also called Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A (trastuzumab + utomilumab) | Experimental | 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). Receives: Drug: Utomilumab; Drug: Trastuzumab |
| Cohort 1B (trastuzumab + utomilumab) | Experimental | Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. Receives: Drug: Utomilumab; Drug: Trastuzumab |
| Cohort 2A (ado-trastuzumab emtansine + utomilumab) | Experimental | Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks. Receives: Drug: Utomilumab; Drug: Ado-Trastuzumab Emtansine |
| Cohort 2B (ado-trastuzumab emtansine + utomilumab) | Experimental | Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks. Receives: Drug: Utomilumab; Drug: Ado-Trastuzumab Emtansine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicities (DLTs)
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.
Measured: 6 weeks
Secondary outcomes (6)
Objective Tumor Response (ORR)
Objective 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.
Measured: 3 months
Time-to-tumor Response (TTR)
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).
Measured: 3 months
Duration of Response (DoR)
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).
Measured: up to 260 weeks
Progression-free Survival (PFS)
Progression-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.
Measured: 128 weeks
Adverse Events by Severity Grade 1 to 5
Adverse 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.
Measured: Up to 128 weeks
Adverse Event Relationship to Study Drugs
Adverse 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.
Measured: Up to 128 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start30 Oct 2017
- Primary completion15 Feb 2021
- Study completion14 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HER2 Positive Breast CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- George W. Sledge Jr.
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, George W. Sledge Jr., Stanford University
- Investigators
- George Sledge, MD, Principal investigator, Stanford Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03364348
- Sponsor's protocol ID
- IRB-37299
- Other IDs
- NCI-2016-01881, BRS0070
- Status last verified
- Sep 2022
- First submitted
- 10 Nov 2017
- Last updated
- 19 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1B Dose Escalation Trial of Human Anti 4 1BB Agonistic Antibody Utomilumab (PF 05082566) in Combination With Ado Trastuzumab Emtansine or Trastuzumab in Patients With HER2 Postive Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT03364348
- Acronym / sponsor ID
- IRB-37299
- Conditions
- HER2 Positive Breast Carcinoma, Recurrent Breast Carcinoma, Stage III Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- George W. Sledge Jr.University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Oct 2017 (actual)
- Primary completion
- 15 Feb 2021 (actual)
- Study completion
- 14 Feb 2022 (actual)
- First posted
- 6 Dec 2017 (actual)
- Results
- Posted 19 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Monoclonal antibodies, such as utomilumab, trastuzumab emtansine, and trastuzumab may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVE:
Estimate the maximum tolerated dose (MTD) and determine the recommended dose (RP2D) of utomilumab in combination with ado-rastuzumab emtansine (T-DM1) or trastuzumab in subjects with HER2-positive advanced breast cancer.
SECONDARY OBJECTIVES:
- Determine the objective tumor response (ORR)
- Determine the time to tumor response (TTR)
- Determine the duration of response (DR)
- Determine progression free survival (PFS)
- Assess the safety and tolerability of utomilumab in combination with ado-trastuzumab emtansine or trastuzumab
OUTLINE: Patients are randomized to 1 of 2 cohorts.
COHORT 1: Dose 1: Utomilumab 20 mg IV + ado-trastuzumab emtansine (T-DM1) 3.6 mg/kg IV every 3 weeks. Dose 2: Dose Level 2 - Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks
COHORT 2: Dose 1: Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. Dose Level 2 - Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A (trastuzumab + utomilumab) | Experimental | Drug: Utomilumab, Drug: TrastuzumabUtomilumab 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) | Experimental | Drug: Utomilumab, Drug: TrastuzumabUtomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. |
| Cohort 2A (ado-trastuzumab emtansine + utomilumab) | Experimental | Drug: Utomilumab, Drug: Ado-Trastuzumab EmtansineUtomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks. |
| Cohort 2B (ado-trastuzumab emtansine + utomilumab) | Experimental | Drug: Utomilumab, Drug: Ado-Trastuzumab EmtansineUtomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- History of biopsy proven HER2 overexpressing breast cancer and radiographic evidence of metastatic disease, or locally recurrent unresectable disease. The HER2 status can be determined either by immunohistochemistry (IHC) [IHC score, 3+] or by fluorescence in situ hybridization (FISH) [as defined by HER2/CEP 17 ratio ≥ 2.0, or HER2 copy number ≥ 6], or as otherwise defined by 2018 ASCO/CAP guidelines.
- Cohort 1 subjects must have received trastuzumab and a taxane separately or in combination (those who previously received ado-trastuzumab emtansine may accrue to Cohort 2).
- Subjects in Cohort 2 must have received at least 1 prior therapy including ado-trastuzumab emtansine.
- Subjects who discontinued prior trastuzumab or ado trastuzumab emtansine due to progressive or refractory disease are eligible for enrollment
- Available tumor samples. For eligibility, if no unstained slides remain, stained pathology slides may be reviewed at the treating institution. However, a tumor sample is required for research evaluations per the following (any of Item 1; 2; or 3, in order of preference).
Key exclusion criteria (25 listed)
- Previously discontinued either trastuzumab or ado trastuzumab emtansine due to intolerance.
- Received any other investigational agents within 30 days of registration.
- Central nervous system (CNS) metastases, unless previously treated by either radiation therapy and/or surgical resection, clinically stable for at least 60 days and on a stable corticosteroid dose of ≤ 4 mg/day decadron (or equivalent steroid regimen) for at least 1 month. Subjects with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply:
- Therapy has been administered (surgery and/or radiation therapy);
- There is no additional treatment planned for brain metastases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UtomilumabAlso: 4-1BB Agonist Monoclonal Antibody PF-05082566, PF-05082566, PF-2566Given IV | Drug | Cohort 1A (trastuzumab + utomilumab), Cohort 1B (trastuzumab + utomilumab), Cohort 2A (ado-trastuzumab emtansine + utomilumab), Cohort 2B (ado-trastuzumab emtansine + utomilumab) |
| TrastuzumabAlso: ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2Given IV | Drug | Cohort 1A (trastuzumab + utomilumab), Cohort 1B (trastuzumab + utomilumab) |
| Ado-Trastuzumab EmtansineAlso: Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020Given IV | Drug | Cohort 2A (ado-trastuzumab emtansine + utomilumab), Cohort 2B (ado-trastuzumab emtansine + utomilumab) |
Primary outcome
Dose-limiting Toxicities (DLTs)
Time frame: 6 weeks
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.
6 secondary outcomes
Objective Tumor Response (ORR)
Time frame: 3 months
Time-to-tumor Response (TTR)
Time frame: 3 months
Duration of Response (DoR)
Time frame: up to 260 weeks
Progression-free Survival (PFS)
Time frame: 128 weeks
Adverse Events by Severity Grade 1 to 5
Time frame: Up to 128 weeks
Adverse Event Relationship to Study Drugs
Time frame: Up to 128 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Sledge, MD principal investigator
Stanford Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Utomilumab, Trastuzumab and Ado-Trastuzumab Emtansine in people with HER2 Positive Breast Carcinoma and Recurrent Breast Carcinoma, run by George W. Sledge Jr. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicities (DLTs) (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2022.