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Trial record 2 of 2 for:    "Tonsil Cancer" | "Antibodies"

Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene

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ClinicalTrials.gov Identifier: NCT03602079
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Klus Pharma Inc.

Brief 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. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer HER2 Gene Mutation HER-2 Gene Amplification HER2 Positive Gastric Cancer Salivary Gland Cancer Salivary Gland Tumor Salivary Gland Carcinoma Salivary Gland Neoplasms Lung Cancer Colo-rectal Cancer Rare Diseases Solid Tumor Recurrent Gastric Cancer Recurrent Colon Cancer Recurrent Breast Cancer Head and Neck Cancer Head and Neck Carcinoma Bladder Cancer Cervical Cancer Liver Cancer Bile Duct Cancer Urologic Cancer Pancreatic Cancer Prostate Cancer Recurrent Prostate Cancer Rectal Cancer Recurrent Ovarian Carcinoma Recurrent Renal Cell Cancer Rectal Cancer Stage II Rectal Cancer Stage I Rectal Cancer Stage III Skin Cancer Mouth Cancer Lip Cancer Stage I Tongue Cancer Breast Neoplasm Malignant Primary Larynx Cancer Tonsil Cancer Palate Cancer Mucoepidermoid Carcinoma Primary Peritoneal Carcinoma Mucinous Adenocarcinoma Gastric Mucinous Breast Cancer Recurrent Cholangiocarcinoma Drug: A166 Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 16, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Phase I: Dose Escalation
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
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

Experimental: Phase II: • Cohort 1
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.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

Experimental: Phase II: • Cohort 2
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.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

Experimental: Phase II: • Cohort 3
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.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

Experimental: Phase II: • Cohort 4
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.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.




Primary Outcome Measures :
  1. 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

  2. Phase II: Percentage of patients with an Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)] [ Time Frame: 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 ]
    Objective Response Rate as determined by RECIST which will be complete response (CR) + partial response (PR)


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Phase II: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ 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 ]
  5. Phase II: Duration of response (DOR) in patients who responded as determined by RECIST [ 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 ]
  6. Phase II: 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 ]
  7. Phase II: Progression Free Survival (PFS) [ Time Frame: 2 years 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 ]
    Kaplan Meier Curve for survival without progression in patients who responded to treatment

  8. Phase II: Overall Survival (OS) [ Time Frame: 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 ]
    Kaplan Meier Curve for survival in all enrolled patients

  9. Phase I and II: Phase I and II Maximum observed serum or plasma concentration (Cmax). [ Time Frame: 84 Days from date of first dose ]
  10. Phase I and II: Clearance (CL). [ Time Frame: 84 Days from date of first dose ]
  11. Phase I and II: Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]). [ Time Frame: 84 Days from date of first dose ]
  12. Phase I and II: Terminal phase elimination half life (t½). [ Time Frame: 84 Days from date of first dose ]
  13. Phase I and II: Volume of distribution at terminal phase (Vz). [ Time Frame: 84 Days from date of first dose ]
  14. Phase I and II: Volume of distribution at steady state (Vss). [ Time Frame: 84 Days from date of first dose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Phase I

Patients must meet the following criteria for inclusion into the study:

  1. Patients must be able to provide documented voluntary informed consent.
  2. Male or female patient ≥ 18 years.
  3. Histologically documented, incurable, locally advanced or metastatic cancer.
  4. 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.
  5. Patients should have no available therapy likely to convey clinical benefit.
  6. Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
  7. 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).
  8. 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.
  9. ECOG Performance Status ≤ 1.
  10. 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.
  11. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Phase II

Patients must meet the following criteria for inclusion into the study:

  1. Patients must be able to provide documented voluntary informed consent.
  2. Male or female patient ≥ 18 years.
  3. Histologically documented, incurable, locally advanced or metastatic cancer.
  4. 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.
  5. Regarding previous therapy:

    5.1. Cohort 1: HER2 positive (IHC 2+ with FISH confirmation and Immunohistochemistry (IHC 3+) breast cancer: patients should have progressed after at least 2 previous HER2 directed regimens in metastatic disease with approved therapies.

    5.2. Cohort 2: HER2 positive (IHC 2+ with FISH confirmation and IHC 3+) gastric cancer: patients should have progressed after at least 1 previous HER2 directed regimens in metastatic disease with approved therapies.

    5.3. Cohort 3: HER2 low expressing (IHC 1+ and IHC 2+ without FISH confirmation) breast cancer: patients should have no available therapy likely to convey clinical benefit.

    5.4. Cohort 4: all cancers other than breast cancer with low HER2 expression (IHC 1+ and IHC 2+ without FISH confirmation) and HER2 positive (IHC 2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer: patients should have no available therapy likely to convey clinical benefit.

  6. Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
  7. 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).
  8. 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.
  9. ECOG Performance Status ≤ 1.
  10. 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.
  11. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Exclusion Criteria:

Phase I:

  1. 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).
  2. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
  3. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
  4. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
  5. Require supplemental oxygen for daily activities.
  6. Documented Grade ≥ 2 peripheral neuropathy.
  7. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
  8. Any experimental therapy within 4 weeks of first infusion of study drug.
  9. Any major surgical procedure within 4 weeks of first infusion of study drug.
  10. 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.
  11. Have known prior positive test results for human immunodeficiency virus.
  12. Uncontrolled hypertension or diabetes.
  13. Pregnancy or lactation.
  14. Resting corrected QT interval (QTc) > 470 ms at baseline.
  15. Left ventricular ejection fraction (LVEF) < 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  16. Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.

Phase II:

  1. Any patient who was treated in the Phase I part of this study.
  2. 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).
  3. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
  4. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
  5. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
  6. Require supplemental oxygen for daily activities.
  7. Documented Grade ≥ 2 peripheral neuropathy.
  8. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
  9. Any experimental therapy within 4 weeks of first infusion of study drug.
  10. Any major surgical procedure within 4 weeks of first infusion of study drug.
  11. 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.
  12. Have known prior positive test results for human immunodeficiency virus.
  13. Uncontrolled hypertension or diabetes.
  14. Pregnancy or lactation.
  15. Resting QTc > 470 ms at baseline.
  16. LVEF < 45% determined by ECHO or MUGA scan.
  17. Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602079


Contacts
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Contact: Clinical Trials Info at Kluspharma 609-662-1913 Clinicaltrialinfo@kluspharma.com

Locations
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United States, Florida
Florida Cancer Specialists & Research Institute Recruiting
Sarasota, Florida, United States, 34232
Contact: Donna L Jones, BSN, RN, OCN,    941-377-9993      
United States, Massachusetts
Beth Israel Deaconess Medical Center Cancer Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Cassandra Cruz    617-975-7411    clcruz@bidmc.harvard.edu   
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Valerie Davis    313-576-9370    davisv@karmanos.org   
United States, New York
Clinical Research Alliance, Inc. Recruiting
Lake Success, New York, United States, 11042
Contact: Colleen Kats       ckats@researchcra.com   
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Dana Suters         
Contact    405-271-8778    SCC-Clinical-Trials-Office@ouhsc.edu   
United States, Oregon
Providence Cancer Institute Recruiting
Portland, Oregon, United States, 97213
Contact: Christina Lopez         
Contact    503-215-2614    Christina.Lopez4@providence.org   
United States, Texas
Mary Crowley Cancer Research Centers - Medical City Recruiting
Dallas, Texas, United States, 75230
Contact: Amy Jordan    972-566-3000    referral@marycrowley.org   
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jordi Rodon Ahnert, M.D., PhD    713-563-1930      
South Texas Accelerated Research Therapeutics, LLC (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265    isabel.jimenez@startsa.com   
United States, Virginia
Virginia Cancer Specialist Recruiting
Fairfax, Virginia, United States, 22031
Contact: Alexander Spira, MD, PhD,FACP    703-280-5390    Alexander.Spira@usoncology.com   
Sponsors and Collaborators
Klus Pharma Inc.
Investigators
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Study Chair: Jordi Rodon Ahnert, MD, PhD MD Anderson

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Responsible Party: Klus Pharma Inc.
ClinicalTrials.gov Identifier: NCT03602079     History of Changes
Other Study ID Numbers: KlusPharma
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Prostatic Neoplasms
Stomach Neoplasms
Rectal Neoplasms
Carcinoma, Renal Cell
Cholangiocarcinoma
Salivary Gland Neoplasms
Bile Duct Neoplasms
Carcinoma, Mucoepidermoid
Tongue Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Colorectal Neoplasms
Laryngeal Neoplasms
Mouth Neoplasms
Lip Neoplasms
Urologic Neoplasms
Tonsillar Neoplasms
Rare Diseases
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
Skin Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases