Clinical trial NCT05187832: A Study of AND019 in Women With ER Positive HER2 Negative Advanced or Metastatic Breast Cancer
Official title: A Phase I Dose Escalation and Dose Expansion Study of AND019 in Patients With Estrogen Receptor Positive Human Epidermal Growth Factor Receptor 2 Negative Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Breast Cancer
Lead sponsor: Kind Pharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2022-01-12
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a first in human dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) activity, and preliminary anti-tumor activity of AND019 in postmenopausal women with advanced or metastatic estrogen receptor (ER)-positive (human epidermal growth factor receptor 2 \[HER2\]-negative) breast cancer.


Eligibility criteria: Key Inclusion Criteria:

1. Postmenopausal women defined as NCCN guideline at the time of informed consent.
2. Histological or cytological confirmation of advanced or metastatic ER+/HER2- breast cancer women who failed standard therapy or for which no standard therapy exists.
3. Prior therapy:

   1. No more than 1 line of chemotherapy for advanced breast cancer
   2. Recurrence or progression on at least one line of endocrine therapy in the advanced or metastatic disease setting and derived a clinical benefit from the endocrine therapy: Recurred or progressed while being treated with adjuvant endocrine therapy for a duration of at least 24 months, or progressed under endocrine therapy for more than 6 months in the advanced or metastatic setting
4. ECOG score 0-1.
5. Minimum life expectancy of a least 3 months as determined by the Investigator.
6. Evaluable disease per RECIST 1.1; for patients consent to tissue biopsy, disease suitable for tumor biopsy.
7. Sufficient bone marrow reserve and organ function.

Key Exclusion Criteria:

1. Previous treatment with any SERDs.
2. Patient any central nervous system metastasis.
3. Prior antitumor therapies:

   1. Received chemotherapies within 3 weeks before the first dose.
   2. Received systemic radiotherapy within 3 weeks before the first dose, or local radiotherapy within 7 days before the first dose
   3. Received other anti-tumor therapy such as endocrine therapy, immunotherapy, and target therapy within 3 weeks or 5 half-lives of the drug before the first dose of the study drug
   4. For bone metastasis, bisphosphonates and local remission therapy are allowed (7 days washout for local radiation therapy).
4. Patient who has participated in any other clinical trials for drugs or treatments within 5 half-lives for a prior investigational drug or 2 weeks from use of an investigational device prior to the first dose of study drug.
5. Patient who had major surgery or significant trauma within 4 weeks prior to the first dose of study drug (excluding needle biopsy), or has scheduled surgery during the study period.
6. Patient with serous unhealable wounds/ulcers/fractures within 4 weeks prior to the first dose of study drug.
7. Patient with adverse reactions to previous anti-tumor treatments who have not yet recovered to grade ≤1 according to CTCAE v5.0. (except for toxicities without safety risks as judged by Investigator, such as alopecia, grade 2 peripheral neuropathy etc.)
8. Patient who has used strong inhibitors or strong inducers of CYP3A, or grapefruit or grapefruit juice within 4 weeks prior to the first dose of study drug.
9. Patient unable to be administered oral medications or any condition that seriously affect digestion in the gastrointestinal tract at the judgement of the Investigator.
10. Patient with active infection within 1 week prior to the first dose of study drug, and currently need systemic anti-infective treatment.
11. Patient has a known history of the following: HIV infection without effective antiretroviral therapy (ART) or acceptable immune function, or syphilis infection, or HBsAg positive HBV or needs prophylaxis therapy or suppressive antiviral therapy before dosing, or has an HCV infection that hasn't completed curative antiviral treatment or with unacceptable viral load.
12. Patient has active cardiac disease or a history cardiac dysfunction.
13. Patient with third spacing that cannot be controlled clinically and is not suitable for the study by the Investigator's judgment.
14. Patient with known history of drug abuse.
15. Patient with mental disorder that, in the opinion of the Investigator, could lead to poor compliance with required study procedures.
16. Patient that cannot tolerate venous blood sampling.
17. Known to have other malignancy within the past 5 years, and is progressing or requires active treatment (except skin basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ who have received potentially radical treatment)

Primary outcomes:
measure: Number of participants with adverse events by severity, according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
timeFrame: From baseline to 12 weeks after the last dose of study treatment (up to 25 months)
measure: PK study of AND019
timeFrame: At predefined timepoints at Day 1, Day 8, Day 15, and Day 22 of Cycle 1, and Day 1 of each cycle starting from Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Determine the RP2D
timeFrame: From baseline to up to the end of Cycle 1 (each cycle is 28 days)
measure: Percentage of Participants with Objective Response
timeFrame: Baseline and every 8 weeks from Cycle 1 Day 1 until Week 24, and then every 12 weeks until end of study treatment (up to 24 months) (each cycle is 28 days)
measure: Clinical Benefit Rate
timeFrame: Baseline and every 8 weeks from Cycle 1 Day 1 until Week 24 (each cycle is 28 days)
measure: Duration of Response
timeFrame: From the first occurrence of a documented objective response until first observation of disease progression or death from any cause on study, whichever occurs first (up to 24 months)
Other outcomes:
measure: Progression free survival
timeFrame: From treatment start date until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
measure: PD study of AND019 in blood samples
timeFrame: At predefined timepoints at baseline, Cycle 1 Day 15, Cycle 2 Day 1, and End of Treatment (up to 2 years) (each cycle is 28 days).
measure: PD study of AND019 in tissue samples
timeFrame: At predefined timepoints at baseline and between Cycle 2 Day 1 to Cycle 3 Day 28 (each cycle is 28 days)
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Kind Pharmaceuticals LLC
name: Yusha Zhu, MD PhD
role: STUDY_DIRECTOR
References: