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NCT Number: NCT03602079

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

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.

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Key information

Conditions

HER2-positive Breast Cancer Adenocarcinoma Adnexal Diseases Bile Duct Cancer Bile Duct Diseases Bile Duct Neoplasms Biliary Tract Diseases Biliary Tract Neoplasms Bladder Cancer Breast Diseases Breast Neoplasm Malignant Primary Breast Neoplasms Carcinoma Carcinoma, Mucoepidermoid Carcinoma, Renal Cell Cervical Cancer Cholangiocarcinoma Colo-rectal Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gonadal Disorders HER-2 Gene Amplification HER2 Gene Mutation HER2 Positive Gastric Cancer Head and Neck Cancer Head and Neck Carcinoma Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Laryngeal Diseases Laryngeal Neoplasms Larynx Cancer Lip Cancer Stage I Lip Diseases Lip Neoplasms Liver Cancer Liver Diseases Liver Neoplasms Lung Cancer Lung Diseases Lung Neoplasms Male Urogenital Diseases Mouth Cancer Mouth Diseases Mouth Neoplasms Mucinous Adenocarcinoma Gastric Mucinous Breast Cancer Recurrent Mucoepidermoid Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Cystic, Mucinous, and Serous Neoplasms, Glandular and Epithelial Oropharyngeal Neoplasms Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Ovarian Diseases Ovarian Neoplasms Palate Cancer Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Pharyngeal Diseases Pharyngeal Neoplasms Primary Peritoneal Carcinoma Prostate Cancer Prostatic Diseases Prostatic Neoplasms Rare Diseases Rectal Cancer Rectal Cancer Stage I Rectal Cancer Stage II Rectal Cancer Stage III Rectal Diseases Rectal Neoplasms Recurrent Breast Cancer Recurrent Colon Cancer Recurrent Gastric Cancer Recurrent Ovarian Carcinoma Recurrent Prostate Cancer Recurrent Renal Cell Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Salivary Gland Cancer Salivary Gland Carcinoma Salivary Gland Diseases Salivary Gland Neoplasms Salivary Gland Tumor Skin Cancer Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Solid Tumor Stomach Diseases Stomach Neoplasms Stomatognathic Diseases Thoracic Neoplasms Tongue Cancer Tongue Diseases Tongue Neoplasms Tonsil Cancer Tonsillar Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Cancer Urologic Diseases Urologic Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Florida Cancer Specialists & Research Institute, Sarasota, Florida, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.
  • 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.

Exclusion criteria

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.
  • 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.

Treatment and study plan

A166

Drug

A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

Primary outcomes

  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

Secondary outcomes

  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 I Maximum observed serum or plasma concentration (Cmax).

    Time frame: 84 Days from date of first dose

  5. Phase I Clearance (CL).

    Time frame: 84 Days from date of first dose

  6. 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

  7. Phase I Terminal phase elimination half life (t½).

    Time frame: 84 Days from date of first dose

  8. Phase I Volume of distribution at terminal phase (Vz).

    Time frame: 84 Days from date of first dose

  9. Phase I Volume of distribution at steady state (Vss).

    Time frame: 84 Days from date of first dose

Sponsors and collaborators

Lead sponsor

Klus Pharma Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Jul 26, 2018
Registry last updated
Aug 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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