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

Learn more about:
Related Clinical Trial
Oral Cancer Awareness in Egypt Predictive Value of GOCCLES® Device for Early Diagnosis of Oral Potentially Malignant Disorders Therapeutic Efficacy of Quercetin Versus Its Encapsulated Nanoparticle on Tongue Squamous Cell Carcinoma Cell Line Mandibular Reconstruction Preplanning (ViPMR) the Oncogenic Potential of Salivary miRNA-93 and miRNA-412-3P in Oral Lichen Planus Patients Newer Therapeutic Targets in Head and Neck Cancers Lateral Arm Free Flap for Reconstruction of the Oral Cavity and Head and Neck Soft Tissue Defects. Improved Implant for Reconstruction Purposes After Mandibular Resection Cell-free Tumor DNA in Head and Neck Cancer Patients Exploring the Application Value of PET Molecular Imaging Targeting FAP in Oral Squamous Cell Carcinoma Exfoliated Cytology in Detection of Oral Premalignant and Malignant Lesions The Oral Microbiome in OSCC The Link Between Periodontitis, Smoking and Oral Cancer Research on Optimization and Evaluation of Oral Cancer Screening Methods Low-Cost, Portable Flexible Nasopharyngoscope in Head & Neck Cancers in Low Resource Settings Topical Aldara (Imiquimod) for Oral Cancer Diagnostic Accuracy of Salivary Gamma-synuclein in Oral Malignant and Premalignant Lesions LLL Phototherapy in Oral Lesions Resulting From Anti-neoplastic Treatment Enhancing Self Care Among Oral Cancer Survivors: The Empowered Survival Trial Understanding Non-radiotherapy-based Development of Trismus Use of Ultrasound for Measuring Size of Oral Tongue Cancers Green Tea Mouthwash on the Oral Health Status in Oral Cancer Patients Oral Cancer Screening and Education in Hong Kong Evaluating Oral Visual Inspection in the Control of Oral Cancer Inductive Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients Effects of EMG Visual Feedback for Spinal Accessory Nerve Dysfunction After Neck Dissection: a Randomized Clinical Trial Prevention of Oral DNA Damage by Black Raspberries Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma NBI in Oral Cavity Cancer Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer 18F-FPPRGD2 PET/CT or PET/MRI in Predicting Early Response in Patients With Cancer Receiving Anti-Angiogenesis Therapy Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene Photodynamic Therapy System for Patients With Refractory/Unresponsive Solid Tumors Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma A Longitudinal Study of Plasma EBV DNA in Nasopharyngeal Carcinoma From Both Endemic and Non-Endemic Patient Populations Radiation Therapy and Bortezomib and Cetuximab With or Without Cisplatin to Treat Head and Neck Cancer Physical Activities by Technology Help (PATH) Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC Very Intense Radiotherapy-Chemotherapy Regimen in Advanced HNSCC Role of Neo-adjuvant Chemotherapy in Tongue Preservation in Locally Advanced Squamous Cell Carcinoma of Oral Tongue Study of Pre-operative Combination Therapy With Mogamulizumab and Nivolumab Against Solid Cancer Patients Patient Evaluation for Head and Neck Surgery Branch Studies Complete Decongestive Therapy (CDT) for Treatment of Head and Neck Lymphedema Neoadjuvant Erbitux Based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer Quality of Life in Patients Treated for Tongue and/or Jaw Neoplasia Before and After Speech Therapy Prospective Analysis of Robot-Assisted Surgery Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery Extended Follow-Up of Young Women in Costa Rica Who Received Vaccination Against Human Papillomavirus Types 16 and 18 and Unvaccinated Controls Clinical Evaluation of the OncAlert RAPID in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making Neo-adjuvant Erbitux-based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer Cigarette Smoking and Oral Microbiota Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma Therapeutic Effect Of Luteolin Natural Extract Versus Its Nanoparticles On Tongue Squamous Cell Carcinoma Cell Line The Role of Lymphangiogenesis in Head and Neck Cancer Metastasis Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis. MSOT Using Cetuximab-800CW for Detection of Cervical Lymph Node Metastases Oral Care Protocol for the Management of Chemotherapy and Radiation Therapy-Induced Oral Mucositis Least Invasive Nonlinear Light Microscopy Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN Trismus Trial of Therabite vs Wooden Spatula in Head and Neck Cancer Patients Improving Access to Control of Diseases for Women IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC Submandibular Gland Preservation in Neck Dissection uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer Postoperative Radiotherapy According to Molecular Analysis of Surgical Margins of Oral and Oropharyngeal SCC Autofluorescence Detection of Oral Malignancies and Database and Biospecimen Collection to Identify Biomarkers of Head and Neck Tumor Progression The Use of Functional Confections in Promoting Oral Health The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma The Study of p62/SQSTM1 as a Malignant Transformation Marker for Oral Potentially Malignant Disorders and a Prognostic Marker for Oral Squamous Cell Carcinoma Evaluation of the Photobiomodulation Using LED Lamp for Curative Treatment of Radio-induced Mucositis. Spectroscopy for Diagnostic Assessment of Oral Mucosal Lesions Wild Type p53 Adenovirus for Oral Premalignancies Acupuncture Effect on Digestion in Critically Ill Post-Operative Oral and Hypo-pharyngeal Cancer Patients Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions Trial of IIb Preserving Neck Dissection Expression of Hypoxia-Inducible Factor-α in Oral Precancers and Cancers Diagnosis of Oral Precancers and Cancers Using Optic Coherence Tomography Innovative Approach to Triage Oral Precancer The Role of SDF-1/CXCR4 in Metastasis of Oral Squamous Cell Carcinoma Rehabilitation Outcomes in Head and Neck Survivors Evaluation of a Multispectral Vision Enhancement System for Assessment of Oral Mucosal Lesions The Relation of Microtubule-Associated Protein 2 and Cell Migration Sensitivity and Specificity of Serum and Salivary CYFRA21-1 in the Detection of Malignant Transformation in Oral Potentially Malignant Mucosal Lesions (Diagnostic Accuracy Study) Prosthesis Guided Speech Rehabilitation of T1/T2 Cancers of the Tongue Oral Pathology Asynchronous Telementoring Pilot Study Polarized Reflectance Spectroscopy for Oral Lesions A Study of the Effects of PEITC on Oral Cells With Mutant p53 Diagnostic Accuracy of Salivary DNA Integrity Index in Oral Malignant and Premalignant Lesions Analysis of the Variation in Caspase-8 Availability and Cleavage in Oral Squamous Cell Carcinoma The Role of microRNA-29b in the Oral Squamous Cell Carcinoma Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer – COOLS TRIAL Assessment of Mandibular Bone Invasion With MRI Using SWIFT Effect of FDG-PET/CT for Simulation and Radiation Treatment Planning in Oral Cancer Patients Epstein-Barr Detection in Oral Cancer Workplace Tobacco Cessation And Oral Cancer Screening Study Low-cost Enabling Technology for Image-guided Photodynamic Therapy (PDT) of Oral Cancer Cancer. Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity Personalized Survivor Care Plan for Oral Cancer Patients-Effects on Physical-Psychological Functions and Return-to-Work Dental Hygienists and Dentists as Providers of Oral Mucosa Screening and Brush Biopsies Effects of Mouth-opening Training on the Maximum Interincisal Opening Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer Oral State of Patients Affected by an Oral Cancer Before and After Radiotherapy – 3-years Prospective Study Erlotinib Prevention of Oral Cancer (EPOC) Oral Cancer Screening in Mumbai, India by Primary Health Care Workers Study on the Carcinogenesis of Gα12 in Oral Cancer, and the Treatment of Oral Cancer Using Ga12 Inhibitor. The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor Study on the Carcinogenesis of SOX-9 in Oral Cancer, and Chemopreventive Possibility for the Treatment of Oral Cancer. Validation of DNA Methylation Biomarkers for Oral Cancer Detection Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study Rehabilitation Outcomes of Shoulder Function in Oral Cancer Survivors Cancer Survivors Behavior Change on Oral Cancer Patients After a Localized Behavior Change Model Intervention Expression of VEGF-C and VEGF-CR in Oral Cancers and Premalignant Lesions PET/CT and Sentinel Node in Oral Cancer Validation of DNA Methylation Biomarkers for Oral Cancer Detection Web-based Education on Oral Cancer for Primary Care Physicians in Ohio Analysis Of Sensory Recovery Of Donor Size And Quality Life In Oral Cancer Patients Using an APP in Post Oral Cancer Surgery to Affect Patients’ Needs and Quality of Life.

Brief Title

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

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

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.

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 Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Phase I: Maximum Tolerated Dose

Secondary Outcome

 Phase I: Number of patients with Dose Limiting Toxicities


HER2-positive Breast Cancer



Study Arms / Comparison Groups

 Phase I: Dose Escalation
Description:  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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

July 16, 2018

Completion Date

December 2022

Primary Completion Date

March 31, 2022

Eligibility 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.

        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

          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.




18 Years - N/A

Accepts Healthy Volunteers



Jordi Rodon Ahnert, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Klus Pharma Inc.

Study Sponsor

Jordi Rodon Ahnert, MD, PhD, Study Chair, MD Anderson

Verification Date

July 2022