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A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KW-2450 in Combination With Lapatinib and Letrozole in Subjects With Advanced or Metastatic Breast Cancer Whose Tumors Overexpress HER2

Phase 1/Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KW-2450 in Combination With Lapatinib and Letrozole in Subjects With Advanced or Metastatic Breast Cancer Whose Tumors Overexpress HER2

This open-label, sequential, ascending, multi-dose, Phase 1/2 study will enroll up to 198
post-menopausal subjects with advanced or metastatic breast cancer whose tumors overexpress
HER2. Subjects at each dose level will receive KW-2450 orally, on a continuous daily
schedule in combination with lapatinib and letrozole.

In the Phase 1 portion of the study, dose escalation may proceed once ≥ 3 subjects have
completed Day 30. The safety of each dose level will be established prior to enrollment of
subjects in the next dose level. Dose escalation will proceed sequentially. Up to 6 subjects
may be enrolled at each dose level. Enrollment will proceed until the MTD has been
established or the highest dose level has been reached.

The Phase 2 portion of the trial will enroll 168 additional subjects. The dose level will be
based on overall safety and tolerability assessments from the Phase 1 portion of the study.
The subjects will be randomized into two treatment arms (1) Arm A, KW-2450 plus lapatinib
plus letrozole: (2) Arm B, lapatinib plus letrozole.

Inclusion Criteria

Inclusion Criteria

1. Histopathologically or cytologically confirmed, advanced or metastatic breast cancer
(stage IIIb, IIIc or IV disease) including inflammatory breast cancer or inoperable
locally advanced disease.

2. Documented ErbB2 overexpression

3. Estrogen receptor positive (ER+) and/or progesterone positive (PgR+) tumors

4. Measurable or non-measurable disease according to Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 Criteria

5. A life expectancy of > 3 months for Phase 1 and > 6 months for Phase 2

6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study
entry in Phase 1 and ≤ 1 in Phase 2;

7. Normal cardiac ejection fraction

8. Adequate hematologic, hepatic and renal function

9. Post-menopausal female (defined as the absence of a menstrual cycle for at least 12
consecutive months) or male subjects ≥ 18 years of age.

10. Sign an IRB or EC approved informed consent

Exclusion Criteria

1. Type 1 diabetes or uncontrolled Type 2 diabetes

2. Subjects showing clinical evidence or with a history of cataract(s), proliferate
retinopathy or significant macular edema

3. Subjects with abnormal free T4 values and a history or evidence of thyroid disease

4. Subjects who are unable or unwilling to take metformin

5. Uncontrolled intercurrent illness

6. Known or suspected human immunodeficiency virus (HIV) infection or hepatitis B or C

7. Subjects with inflammatory diseases of the gastrointestinal tract

8. History of other malignancy. Subjects who have been disease free for 5 years, or
subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible;

9. Subjects with extensive symptomatic visceral disease including hepatic involvement
and pulmonary lymphangitic spread of tumor

10. A history of prior treatment with other agents specifically targeting IGFRs

11. Subjects who require pharmacological doses of glucocorticoids beyond replacement
doses. The use of topical, intra-ocular or inhalation glucocorticoids is permitted

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To establish the safety, tolerability, and recommended Phase 2 dose of KW-2450 administered in combination with lapatinib and letrozole in subjects with previously treated or untreated advanced breast cancer.

Outcome Time Frame:

30 Days

Safety Issue:


Principal Investigator

Michael Kurman, MD

Investigator Role:

Study Director

Investigator Affiliation:

Kyowa Hakko Kirin Pharma, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

December 2012

Related Keywords:

  • Breast Cancer
  • advanced or metastatic breast cancer
  • Breast Neoplasms



MD Anderson Cancer Center Houston, Texas  77030-4096
Sylvester Comprehensive Cancer Center Miami, Florida  
Breastlink Research Group Long Beach, California  90250
Associates in Hematology-Oncology Los Angeles, California  90057
Clinical Oncology Associates Farmington Hills, Michigan  48336