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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03602079
• Other study ID #: KlusPharma
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 16, 2018
• Est. completion date: January 12, 2022

Study information

• Verified date: August 2023
• Source: Klus Pharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 12, 2022
• Est. primary completion date: January 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Adenocarcinoma, Mucinous
• Bile Duct Cancer
• Bile Duct Neoplasms
• Bladder Cancer
• Breast Neoplasm Malignant Primary
• Breast Neoplasms
• Carcinoma
• Carcinoma, Renal Cell
• Cervical Cancer
• Cholangiocarcinoma
• Colo-rectal Cancer
• Cystadenocarcinoma
• Head and Neck Cancer
• Head and Neck Carcinoma
• HER-2 Gene Amplification
• HER2 Gene Mutation
• HER2 Positive Gastric Cancer
• HER2-positive Breast Cancer
• Laryngeal Neoplasms
• Larynx Cancer
• Lip Cancer Stage I
• Lip Neoplasms
• Liver Cancer
• Lung Cancer
• Mouth Cancer
• Mouth Neoplasms
• Mucinous Adenocarcinoma Gastric
• Mucinous Breast Cancer Recurrent
• Mucoepidermoid Carcinoma
• Neoplasms
• Palate Cancer
• Pancreatic Cancer
• Primary Peritoneal Carcinoma
• Prostate Cancer
• Prostatic Neoplasms
• Rare Diseases
• Rectal Cancer
• Rectal Cancer Stage I
• Rectal Cancer Stage II
• Rectal Cancer Stage III
• Rectal Neoplasms
• Recurrence
• Recurrent Breast Cancer
• Recurrent Colon Cancer
• Recurrent Gastric Cancer
• Recurrent Ovarian Carcinoma
• Recurrent Prostate Cancer
• Recurrent Renal Cell Cancer
• Salivary Gland Cancer
• Salivary Gland Carcinoma
• Salivary Gland Neoplasms
• Salivary Gland Tumor
• Skin Cancer
• Solid Tumor
• Stomach Neoplasms
• Tongue Cancer
• Tongue Neoplasms
• Tonsil Cancer
• Urologic Cancer
• Urologic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center Cancer Center	Boston	Massachusetts
United States	Mary Crowley Cancer Research Centers - Medical City	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Clinical Research Alliance, Inc.	Lake Success	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Providence Cancer Institute	Portland	Oregon
United States	South Texas Accelerated Research Therapeutics, LLC (START)	San Antonio	Texas
United States	Florida Cancer Specialists & Research Institute	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Klus Pharma Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Maximum Tolerated Dose	Number of patients with dose limiting toxicities	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	Phase I: Number of patients with Dose Limiting Toxicities		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	Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.		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
Secondary	Phase I: Number of participants who developed measurable anti-drug antibodies		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	Phase I Maximum observed serum or plasma concentration (Cmax).		84 Days from date of first dose
Secondary	Phase I Clearance (CL).		84 Days from date of first dose
Secondary	Phase I Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-8]).		84 Days from date of first dose
Secondary	Phase I Terminal phase elimination half life (t½).		84 Days from date of first dose
Secondary	Phase I Volume of distribution at terminal phase (Vz).		84 Days from date of first dose
Secondary	Phase I Volume of distribution at steady state (Vss).		84 Days from date of first dose