HER2-positive Breast CancerPhase 1/2NCT03602079
Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
A Phase 1/2 study testing A166 in people with HER2-positive Breast Cancer and HER2 Gene Mutation, run by Klus Pharma Inc. at 10 sites in United States.
Trial summary
Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, HER2 Gene Mutation, HER-2 Gene Amplification
- What is being tested?
- A166
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 10 sitesUnited States
- Study dates
- 16 Jul 2018to 12 Jan 2022
- Phase
- Phase 1/2
- 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
- Phase I
- Patients must meet the following criteria for inclusion into the study:
- Patients must be able to provide documented voluntary informed consent.
- Male or female patient ≥ 18 years.
- Histologically documented, incurable, locally advanced or metastatic cancer.
- Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.
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- Patients should have no available therapy likely to convey clinical benefit.
- Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
- Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
- Creatinine clearance ≥ 50 mL/min calculated by Cockroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
- ECOG Performance Status ≤ 1.
- Women of childbearing potential and men must agree to use an approved method of birth control (e.g., hormonal, barrier) while receiving study drug, and for at least 7 months after the last dose of study drug. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
- Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.
Who cannot join
- Phase I:
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
- History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
- History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
- Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
- Require supplemental oxygen for daily activities.
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- Documented Grade ≥ 2 peripheral neuropathy.
- Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
- Any experimental therapy within 4 weeks of first infusion of study drug.
- Any major surgical procedure within 4 weeks of first infusion of study drug.
- Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
- Have known prior positive test results for human immunodeficiency virus.
- Uncontrolled hypertension or diabetes.
- Pregnancy or lactation.
- Resting corrected QT interval (QTc) > 470 ms at baseline.
- Left ventricular ejection fraction (LVEF) < 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
- Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Beth Israel Deaconess Medical Center Cancer Center
Boston, Massachusetts, 02215
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, 75230
Karmanos Cancer Institute
Detroit, Michigan, 48201
Virginia Cancer Specialist
Fairfax, Virginia, 22031
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Clinical Research Alliance, Inc.
Lake Success, New York, 11042
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Providence Cancer Institute
Portland, Oregon, 97213
South Texas Accelerated Research Therapeutics, LLC (START)
San Antonio, Texas, 78229
Florida Cancer Specialists & Research Institute
Sarasota, Florida, 34232
About this study
Official title: A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.
Read the detailed description
This is an open-label, Phase I-II, first-in-human (FIH) study for A166 as monotherapy in HER2-expressing patients who progressed on or did not respond to available standard therapies. Patients enrolled in this Phase III study must have documented HER2 positivity defined as positive on in situ hybridization (ISH) or next-generation sequencing (NGS) or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease. Patients will receive study drug as a single IV infusion at the prescribed dose level in each treatment cycle. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).
- Conditions
- HER2-positive Breast Cancer, HER2 Gene Mutation, HER-2 Gene Amplification, HER2 Positive Gastric Cancer, Salivary Gland Cancer, Salivary Gland Tumor
- Being tested
- A166
- Medical subject headings
- Salivary Gland Neoplasms, Lung Neoplasms, Colonic Neoplasms, Rare Diseases, Stomach Neoplasms, Breast Neoplasms, Head and Neck Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A166Drug
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Dose Escalation | Experimental | Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166 Receives: Drug: A166 |
| Phase II: • Cohort 1 | Experimental | HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose. Receives: Drug: A166 |
| Phase II: • Cohort 2 | Experimental | HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose. Receives: Drug: A166 |
| Phase II: • Cohort 3 | Experimental | HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose. Receives: Drug: A166 |
| Phase II: • Cohort 4 | Experimental | All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose. Receives: Drug: A166 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Maximum Tolerated Dose
Number of patients with dose limiting toxicities
Measured: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes (9)
Phase I: Number of patients with Dose Limiting Toxicities
Measured: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Measured: Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants who developed measurable anti-drug antibodies
Measured: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I Maximum observed serum or plasma concentration (Cmax).
Measured: 84 Days from date of first dose
Phase I Clearance (CL).
Measured: 84 Days from date of first dose
Phase I Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]).
Measured: 84 Days from date of first dose
Phase I Terminal phase elimination half life (t½).
Measured: 84 Days from date of first dose
Phase I Volume of distribution at terminal phase (Vz).
Measured: 84 Days from date of first dose
Phase I Volume of distribution at steady state (Vss).
Measured: 84 Days from date of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start16 Jul 2018
- Primary completion12 Jan 2022
- Study completion12 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Klus Pharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jordi Rodon Ahnert, MD, PhD, Study chair, MD Anderson
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03602079
- Sponsor's protocol ID
- KlusPharma
- Status last verified
- Aug 2023
- First submitted
- 6 Jul 2018
- Last updated
- 3 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies
- ClinicalTrials.gov ID
- NCT03602079
- Acronym / sponsor ID
- KlusPharma
- Conditions
- HER2-positive Breast Cancer, HER2 Gene Mutation, HER-2 Gene Amplification, HER2 Positive Gastric Cancer, Salivary Gland Cancer, Salivary Gland Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Klus Pharma Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Jul 2018 (actual)
- Primary completion
- 12 Jan 2022 (actual)
- Study completion
- 12 Jan 2022 (actual)
- First posted
- 26 Jul 2018 (actual)
- 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.
Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.
Detailed description
This is an open-label, Phase I-II, first-in-human (FIH) study for A166 as monotherapy in HER2-expressing patients who progressed on or did not respond to available standard therapies. Patients enrolled in this Phase III study must have documented HER2 positivity defined as positive on in situ hybridization (ISH) or next-generation sequencing (NGS) or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease. Patients will receive study drug as a single IV infusion at the prescribed dose level in each treatment cycle. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase I: Dose Escalation | Experimental | Drug: A166Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166 |
| Phase II: • Cohort 1 | Experimental | Drug: A166HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose. |
| Phase II: • Cohort 2 | Experimental | Drug: A166HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose. |
| Phase II: • Cohort 3 | Experimental | Drug: A166HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose. |
| Phase II: • Cohort 4 | Experimental | Drug: A166All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Phase I
- Patients must be able to provide documented voluntary informed consent.
- Male or female patient ≥ 18 years.
- Histologically documented, incurable, locally advanced or metastatic cancer.
- Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.
Key exclusion criteria (17 listed)
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
- History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
- History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
- Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
- Require supplemental oxygen for daily activities.
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 |
|---|---|---|
| A166A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells. | Drug | Phase I: Dose Escalation, Phase II: • Cohort 1, Phase II: • Cohort 2, Phase II: • Cohort 3, Phase II: • Cohort 4 |
Primary outcome
Phase I: Maximum Tolerated Dose
Time frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Number of patients with dose limiting toxicities
9 secondary outcomes
Phase I: Number of patients with Dose Limiting Toxicities
Time frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time frame: Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants who developed measurable anti-drug antibodies
Time frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I Maximum observed serum or plasma concentration (Cmax).
Time frame: 84 Days from date of first dose
Phase I Clearance (CL).
Time frame: 84 Days from date of first dose
Phase I Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]).
Time frame: 84 Days from date of first dose
Phase I Terminal phase elimination half life (t½).
Time frame: 84 Days from date of first dose
Phase I Volume of distribution at terminal phase (Vz).
Time frame: 84 Days from date of first dose
Phase I Volume of distribution at steady state (Vss).
Time frame: 84 Days from date of first dose
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 3 Aug 2023.
- 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.
Jordi Rodon Ahnert, MD, PhD study chair
MD Anderson
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing A166 in people with HER2-positive Breast Cancer and HER2 Gene Mutation, run by Klus Pharma Inc. at 10 sites 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 13 inclusion and 17 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 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Phase I: Maximum Tolerated Dose (time frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months). 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 3 Aug 2023.