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BRIEF 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

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


  • Org Study ID: KlusPharma
  • Secondary ID:
  • NCT ID: NCT03602079
  • NCT Alias:
  • Sponsor: Klus Pharma Inc. - Industry
  • Source: 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.

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).

Overal Status Start Date Phase Study Type
Recruiting July 16, 2018 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Phase I: Maximum Tolerated Dose

Primary Outcome 1 - 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

Primary Outcome 2 - Measure: Phase II: Percentage of patients with an Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)]

Primary Outcome 2 - 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

Condition:

  • 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

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.

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.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Jordi Rodon Ahnert, MD, PhD

Role: Study Chair

Affiliation: MD Anderson

Overall Contact

Name: Clinical Trials Info at Kluspharma

Phone: 609-662-1913

Email: Clinicaltrialinfo@kluspharma.com

Locations

Facility Status Contact
Florida Cancer Specialists & Research Institute
Sarasota, Florida 34232
United States
Recruiting Donna L Jones, BSN, RN, OCN,
941-377-9993
Beth Israel Deaconess Medical Center Cancer Center
Boston, Massachusetts 02215
United States
Recruiting Cassandra Cruz
617-975-7411
clcruz@bidmc.harvard.edu
Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Not yet recruiting Valerie Davis
313-576-9370
davisv@karmanos.org
Clinical Research Alliance, Inc.
Lake Success, New York 11042
United States
Recruiting Colleen Kats

ckats@researchcra.com
Stephenson Cancer Center
Oklahoma City, Oklahoma 73104
United States
Recruiting Dana Suters

Providence Cancer Institute
Portland, Oregon 97213
United States
Not yet recruiting Christina Lopez

Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas 75230
United States
Recruiting Amy Jordan
972-566-3000
referral@marycrowley.org
The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Yunfang (Jenny) Jiang
713-794-1751
yjiang@mdanderson.org
South Texas Accelerated Research Therapeutics, LLC (START)
San Antonio, Texas 78229
United States
Recruiting Isabel Jimenez, RN, MSN
210-593-5265
isabel.jimenez@startsa.com
Virginia Cancer Specialist
Fairfax, Virginia 22031
United States
Not yet recruiting Alexander Spira, MD, PhD,FACP
703-280-5390
Alexander.Spira@usoncology.com