Solid Tumors That Overexpress HER2 (HER2 Positive)Phase 1NCT02286219
Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors (Anti HER2 Fcab)
A Phase 1 study testing FS102 in people with Solid Tumors That Overexpress HER2 (HER2 Positive), run by Bristol-Myers Squibb at 6 sites in 2 countries.
Trial summary
To evaluate the safety, tolerability, dose limiting toxicity (DLT), and maximum tolerated dose (MTD), of FS102(BMS-986186) when administered intravenously (IV) to subjects with relapsed or refractory solid tumors that overexpress HER2 and who have no standard treatment options. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors That Overexpress HER2 (HER2 Positive)
- What is being tested?
- FS102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 4 Nov 2014to 8 Jun 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Signed written informed consent obtained prior to performing any study procedure, including screening procedures.
- Men and women ≥ 18-years-old on the day of signing informed consent.
- Subjects must have histologically or cytologically confirmed solid tumor malignancy that is unresectable/locally advanced and/or metastatic and for which standard curative or palliative measures are not available or are no longer effective (for all subjects, histologic or cytologic proof of malignancy based on prior primary cancer pathology is acceptable).
- Subjects must have HER2-positive tumors and written clinical pathology report documentation of HER2 status available for Sponsor's Medical Monitor review.
- Assessment of HER2 status in subjects with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (Wolff et al, 2013) as practicable.
- Assessment of HER2 status in subjects with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Rüschoff et al (2012) as practicable.
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- Assessment of HER2 status in subjects with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
- All subjects with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using an assay kit/methodology specifically FDA-approved for their cancer type as practicable.
- Subjects for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without a written report of ISH determined HER2 copy number, provided the investigative site confirms that archival tissue is available.
- Subjects with breast cancer must have been treated with at least two FDA-approved anti-HER2 directed therapies (more than two is also permissible), and subjects with gastric and gastroesophageal junction cancers must have been treated with at least one FDA-approved anti-HER2 directed therapy (more than one is also permissible); and all subjects must have refractory or relapsed/progressive disease during or following their last prior anti-HER2 directed therapy.
- Subjects enrolling in the study who have non-breast, non-gastric, non-gastroesophageal junction cancers do not require any prior treatment with anti-HER2 therapy if there is no FDA-approved anti-HER2 agent for their specific cancer type, but they must have refractory or relapsed/progressive disease during or following their last prior anti-cancer therapy.
- For all subjects, prior post-operative adjuvant administration of anti-HER2 therapy is permissible.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 and estimated life expectancy ≥ 3 months.
- Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m2.
- Adequate organ function as defined below:
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 upper limit of normal (ULN); if liver function abnormalities are due to the underlying malignancy, then AST and ALT must be ≤ 5 ULN;
- Total serum bilirubin ≤ ULN unless due to Gilbert's Syndrome;
- Serum creatinine ≤ 1.25 x ULN; or if serum creatinine > 1.25 ULN, then calculated (Cockcroft-Gault formula, glomerular filtration rate (GFR) ≥ 60 mL/min;
- Hemoglobin ≥ 9.0 g/dL and not requiring > 1 unit red blood cell transfusion per month; subjects receiving therapeutic erythropoietin preparations in accordance with the FDA product label are eligible to enroll;
- Absolute neutrophil count ≥ 1,500/mm3 (not supported by growth factors in the preceding 21 days);
- Platelet count ≥ 100,000/mm3 (without platelet transfusion or growth factor support in the preceding 7 days);
- Activated partial thromboplastin time (aPTT) ≤ 1.25 ULN and international normalized ratio (INR) ≤ 1.3 (unless the subject is receiving therapeutic anticoagulants);
- Left ventricular ejection fraction (LVEF) determined by 2 dimensional echocardiogram (2D Echo) or multi-gated acquisition scan (MUGA) ≥ 50% or ≥ local institutional lower limit normal (LLN) whichever is higher.
- Serum magnesium, calcium, and phosphorus must be within normal reference ranges as per local tests. [If initial screening results are outside of normal reference range, the Investigator may initiate appropriate measures to correct. However administration of FS102 may not proceed until the specified electrolytes have normalized.]
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening for eligibility assessments and enrollment and within 24 hours prior to the start of study drug.
- Women must not be breastfeeding
- WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug FS102 plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug FS102 plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion.
- Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing as described in this section.
- Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly.
- At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below.
Who cannot join
- Primary brain or other central nervous system malignancy.
- Any history of leptomeningeal metastasis.
- Active brain metastasis or treatment for brain metastasis within 1 month of scheduled dosing day 1.
- Dose of corticosteroid, if any, for brain metastasis must be tolerated in terms of glucose tolerance ≤ Grade 2 (symptomatic; dietary modification or oral agent indicated) and hyperglycemia ≤ Grade 2 (fasting glucose value >160 - 250 mg/dL [> 8.9 - 13.9 mmol/L]).
- History of second or other primary cancer with the exception of: 1) curatively treated non-melanomatous skin cancer; 2) curatively treated cervical or breast carcinoma in situ; or 3) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years.
- Receipt of any investigational treatment within 4 weeks of scheduled dosing day 1.
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- Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled dosing day 1.
- Receipt of radiation therapy within 3 weeks of scheduled dosing day 1, unless the radiation comprised a limited field to non-visceral structures (eg, a limb bone metastasis).
- Receipt of treatment with immunotherapy (including interferons, interleukins, immunoconjugates), biological therapies (including monoclonal antibodies or other engineered proteins), targeted small molecules (including but not limited to kinase inhibitors), hormonal therapies (except for gonadotropin releasing hormone agonists/antagonists for prostate cancer which may be continued while on study) within 3 weeks of scheduled dosing day 1.
- Receipt of trastuzumab, pertuzumab, or ado-trastuzumab emtansine within 4 weeks of scheduled dosing day 1.
- Receipt of lapatinib within 7 days of scheduled dosing day 1.
- Is concurrently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo.
- Exclusionary concurrent medical conditions:
- Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 90 mm Hg;
- Myocardial infarction, unstable angina, coronary artery bypass graft, coronary artery angioplasty or stent placement within 12 months before scheduled dosing day 1;
- History of congestive heart failure;
- History of absolute decrease in LVEF of ≥ 16 absolute percentage points, or ≥ 10 absolute percentage points and crossing from > LLN to < LLN on prior anti-HER2 therapy, even if asymptomatic and the LVEF decrease recovered;
- Abnormal 12-lead electrocardiogram (ECG) judged to be clinically significant by the Investigator;
- Hemorrhagic, embolic, or thrombotic stroke within 6 months of scheduled dosing day 1;
- Prior bone marrow or stem cell transplant;
- Previously known infection with human immunodeficiency virus (HIV); or, hepatitis B or C requiring treatment;
- Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2;
- Non-malignant interstitial lung disease;
- Dyspnea of any cause requiring supplemental oxygen therapy;
- Significant traumatic injury or major surgery (major surgery means opening of a body cavity, eg, thoracotomy, laparotomy, laparoscopic organ resection, and major orthopedic procedures, eg, joint replacement, open reduction and internal fixation) within 21 days of scheduled dosing day 1;
- Any other acute or chronic medical or psychiatric condition (including alcohol and illicit substance abuse) or laboratory abnormality that could increase the risk associated with study participation or could interfere with the interpretation of the study results and, in the judgment of the Investigator or Medical Monitor, would render the subject inappropriate for participation in the study.
- Has not recovered from the adverse effects of previous anti-cancer treatments to pre-treatment baseline or Grade 1, except for alopecia, anemia (hemoglobin must meet the present study inclusion criterion), and peripheral neuropathy (which must have recovered to ≤ Grade 2).
- Hypersensitivity/infusion reaction to monoclonal antibodies, other therapeutic proteins, or allergy to any component/excipient of FS102 finished drug product (arginine, glycine, phosphoric acid, or polysorbate 80) and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as anti-histamines, 5-HT3 antagonists, or corticosteroids.
- Subjects who are pregnant or breast feeding.
- Subjects who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Anthony El-Khoueiry, Md
Los Angeles, California, 90033
The West Clinic
Memphis, Tennessee, 38120
Southwest Texas Addiction Research And Tech (Start) Center
San Antonio, Texas, 78229-3900
University of Washington
Seattle, Washington, 98109
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors
To evaluate the safety, tolerability, dose limiting toxicity (DLT), and maximum tolerated dose (MTD), of FS102(BMS-986186) when administered intravenously (IV) to subjects with relapsed or refractory solid tumors that overexpress HER2 and who have no standard treatment options.
Read the detailed description
This is a Phase 1, open-label, multiple dose escalation study in subjects with solid tumors that over express HER2.
Subjects with locally un-resectable and/or metastatic solid cancers that over express human epidermal growth factor tyrosine kinase receptor 2 (HER2) by standard clinical pathology criteria and who have no standard treatment options will be enrolled into a series of escalating dose cohorts.
Within each dose cohort, subjects will receive weekly (± 1 day) or less frequent IV (Q3W) infusions of FS102 during an initial 28-day (4-week) DLT observation period. During the DLT observation period, subjects will be assessed for safety, tolerability, dose limiting toxicity, PK, immunogenicity, and clinical disease response. Following assessment by the Investigator, subjects without clinical disease progression and without unacceptable toxicity will be eligible to continue receiving FS102 for up to six 21 (Q3W) to 28-day (weekly) cycles.
Continuation Phase. Subjects who complete six 21-28-day cycles of treatment will be evaluated for entry into an extended Continuation Phase of the study. Subjects will be eligible for continuation if:
- They demonstrate no evidence of disease progression;
- In the opinion of the Investigator they are deemed reasonably likely to continue to benefit from treatment; and
- They have not experienced any toxicity requiring discontinuation. During the Continuation Phase, subjects will continue to receive FS102 at the same dose they were originally assigned, unless modified downward for earlier toxicity. No dose escalation within subjects will be permitted.
Treatment may continue until one of the following criteria applies:
- Disease progression;
- Intervening illness that prevents further administration of treatment;
- Unacceptable adverse events;
- Significant subject non-compliance with protocol;
- Pregnancy;
- Subject decides to withdraw from study;
- General or specific changes in the subject's condition that render the subject unacceptable for further treatment in the judgment of the Investigator; or
- Sponsor decides to end the study.
- Being tested
- FS102
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FS102Drug
Also called Fcab, Fc region of full immunoglobulin G, subclass 1 [IgG1]
Experimental
| Study group | Role | What they receive |
|---|---|---|
| FS102 | Experimental | Dose escalation of either weekly or Q3W of FS102 Receives: Drug: FS102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events as assessed by NCI Common Toxicity Criteria for Adverse Events CTCAE v3.0
Measured: 1 year
Secondary outcomes (3)
Clinical benefit as assessed by objective response rate
Measured: 1 year
PK profile as assessed by drug levels
Measured: 1 year
Adverse events as assessed by immune response to drug
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2014 (estimated)
- Study start4 Nov 2014
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumors That Overexpress HER2 (HER2 Positive)Studies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02286219
- Sponsor's protocol ID
- CA014-001
- Other IDs
- FS10214100
- Status last verified
- Sep 2017
- First submitted
- 31 Oct 2014
- Last updated
- 18 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors
- ClinicalTrials.gov ID
- NCT02286219
- Acronym / sponsor ID
- CA014-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2014 (actual)
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 7 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety, tolerability, dose limiting toxicity (DLT), and maximum tolerated dose (MTD), of FS102(BMS-986186) when administered intravenously (IV) to subjects with relapsed or refractory solid tumors that overexpress HER2 and who have no standard treatment options.
Detailed description
This is a Phase 1, open-label, multiple dose escalation study in subjects with solid tumors that over express HER2.
Subjects with locally un-resectable and/or metastatic solid cancers that over express human epidermal growth factor tyrosine kinase receptor 2 (HER2) by standard clinical pathology criteria and who have no standard treatment options will be enrolled into a series of escalating dose cohorts.
Within each dose cohort, subjects will receive weekly (± 1 day) or less frequent IV (Q3W) infusions of FS102 during an initial 28-day (4-week) DLT observation period. During the DLT observation period, subjects will be assessed for safety, tolerability, dose limiting toxicity, PK, immunogenicity, and clinical disease response. Following assessment by the Investigator, subjects without clinical disease progression and without unacceptable toxicity will be eligible to continue receiving FS102 for up to six 21 (Q3W) to 28-day (weekly) cycles.
Continuation Phase. Subjects who complete six 21-28-day cycles of treatment will be evaluated for entry into an extended Continuation Phase of the study. Subjects will be eligible for continuation if:
- They demonstrate no evidence of disease progression;
- In the opinion of the Investigator they are deemed reasonably likely to continue to benefit from treatment; and
- They have not experienced any toxicity requiring discontinuation. During the Continuation Phase, subjects will continue to receive FS102 at the same dose they were originally assigned, unless modified downward for earlier toxicity. No dose escalation within subjects will be permitted.
Treatment may continue until one of the following criteria applies:
- Disease progression;
- Intervening illness that prevents further administration of treatment;
- Unacceptable adverse events;
- Significant subject non-compliance with protocol;
- Pregnancy;
- Subject decides to withdraw from study;
- General or specific changes in the subject's condition that render the subject unacceptable for further treatment in the judgment of the Investigator; or
- Sponsor decides to end the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FS102 | Experimental | Drug: FS102Dose escalation of either weekly or Q3W of FS102 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Signed written informed consent obtained prior to performing any study procedure, including screening procedures.
- Men and women ≥ 18-years-old on the day of signing informed consent.
- Subjects must have histologically or cytologically confirmed solid tumor malignancy that is unresectable/locally advanced and/or metastatic and for which standard curative or palliative measures are not available or are no longer effective (for all subjects, histologic or cytologic proof of malignancy based on prior primary cancer pathology is acceptable).
- Subjects must have HER2-positive tumors and written clinical pathology report documentation of HER2 status available for Sponsor's Medical Monitor review.
- Subjects with breast cancer must have been treated with at least two FDA-approved anti-HER2 directed therapies (more than two is also permissible), and subjects with gastric and gastroesophageal junction cancers must have been treated with at least one FDA-approved anti-HER2 directed therapy (more than one is also permissible); and all subjects must have refractory or relapsed/progressive disease during or following their last prior anti-HER2 directed therapy.
Key exclusion criteria (30 listed)
- Primary brain or other central nervous system malignancy.
- Any history of leptomeningeal metastasis.
- Active brain metastasis or treatment for brain metastasis within 1 month of scheduled dosing day 1.
- History of second or other primary cancer with the exception of: 1) curatively treated non-melanomatous skin cancer; 2) curatively treated cervical or breast carcinoma in situ; or 3) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years.
- Receipt of any investigational treatment within 4 weeks of scheduled dosing day 1.
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 |
|---|---|---|
| FS102Also: Fcab, Fc region of full immunoglobulin G, subclass 1 [IgG1]Experimental | Drug | FS102 |
Primary outcome
Adverse events as assessed by NCI Common Toxicity Criteria for Adverse Events CTCAE v3.0
Time frame: 1 year
3 secondary outcomes
Clinical benefit as assessed by objective response rate
Time frame: 1 year
PK profile as assessed by drug levels
Time frame: 1 year
Adverse events as assessed by immune response to drug
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2017.
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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FS102 in people with Solid Tumors That Overexpress HER2 (HER2 Positive), run by Bristol-Myers Squibb at 6 sites in 2 countries.
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 31 inclusion and 30 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 18 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events as assessed by NCI Common Toxicity Criteria for Adverse Events CTCAE v3.0 (time frame: 1 year). 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 18 Sep 2017.