Trial Title:
A Phase I Clinical Trial of FWD1802 in Patients With ER+/HER2- BC.
NCT ID:
NCT06064812
Condition:
Metastatic Breast Cancer
Locally Advanced Breast Cancer
Breast Cancer Stage I
ER+ Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
FWD1802
Description:
Subjects will receive FWD1802 tablets orally according to the overall study design; the
administration scheme is shown above. Subjects will continue to receive FWD1802 until any
of the criteria are met.
Study drugs will be orally administered at the investigational site by site staff at 8 AM
on the morning of the dosing days.
Arm group label:
Part A: Dose Escalation of FWD1802 as a Monotherapy
Arm group label:
Part B- Dose Escalation of FWD1802 in combination with palbocilib
Arm group label:
Part C - Dose Expansion Study
Intervention type:
Drug
Intervention name:
palbocilib
Description:
The palbociclib dose is the fixed approved dose: 125 mg intake daily, for consecutive 21
days then off for 7 days, which composes 28-day treatment cycle, which is consistent with
the 28-day treatment cycle of FWD1802.
Every treatment cycle consists of 28 days.
Arm group label:
Part B- Dose Escalation of FWD1802 in combination with palbocilib
Summary:
This is a phase I open-label dose escalation trial of FWD1802 as monotherapy and in
combination with palbociclib in patients with ER+/HER2- unresectable locally advanced or
metastatic breast cancer The goal of this clinical trial] is to learn about in ER+/HER2-
BC participant population. The main questions it aims to answer are:
- Establish the recommended phase II dose (RP2D) and/or the maximum tolerated dose
(MTD) of FWD1802 as monotherapy and in combination with palbociclib in patients with
ER+/HER2- unresectable locally advanced or metastatic breast cancer.
- Explore the safety and tolerability of FWD1802 as monotherapy and in combination
with Palbociclib.
- Characterise Pharmacokinetics of FWD1802 as monotherapy and in combination with
palbociclib.
- Explore preliminary efficacy signals.
Detailed description:
This is a multiple cohort study, an initial dose escalation phase is designed to confirm
the safe dose of FWD1802 as monotherapy and in combination with Palbociclib.
A Safety Monitoring Committee (SMC) will monitor the safety, tolerability, and PK data
during this phase. Once ascertained, an expansion cohort will be opened to explore the
efficacy of FWD1802 as monotherapy and in combination with Palbociclib.
Part A is an open-label, dose escalation of FWD 1802 as monotherapy . Dose escalation
steps will be determined by the Safety Monitoring Committee (SMC), based on 3+3 rule
except for the accelerated escalation on the 1st dose level. With pharmacokinetic (PK),
pharmacodynamics (PD), efficacy and safety data, SMC will evaluate to guide determination
of potentially effective dose for part B and C.
Part B is an open-label, dose escalation of FWD 1802 in combination with palbociclib
fixed dose. Dose escalation steps will be determined by SMC, based on 3+3 rule. With PK,
PD, efficacy and safety data, SMC will evaluate to guide determination of potentially
effective combination dose.
Part C is an open label , dose expansion of FWD 1802 monotherapy on patients with
ER+/HER2-/ESR1 mutation, no more than 2 dose levels will be evaluated, with 30 patients
at the most in either dose level cohort.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must understand and voluntarily sign the Informed Consent Form (ICF).
2. Patients ≥ 18 years, female.
3. Provision of blood sample to test ESR1 mutation status and for other biomarker
assessment. In part A/B, the ESR1 mutation status will be tested retrospectively; In
part C, only the patients with ESR1 mutation positive is eligible.
4. Documented positive oestrogen receptor status of primary or metastatic tumour
tissue, according to the local laboratory parameters. HER-2 negative. These
laboratory parameters are consistent with accepted diagnostic guidelines such as the
American Society of Clinical Oncology (ASCO) / College of American Pathologists
(CAP) Clinical Practice Guideline for Pathologists estrogen (ER) and progesterone
receptor (PgR) testing in breast cancer (Allison et al., 2020). HER2- defined as an
Immunohistochemistry (IHC) status of 0, 1+ or negative by in situ hybridization
test.
5. Menopausal women according to one of the following criteria:
1. Prior bilateral ovariectomy;
2. Patients ≥ 60 years of age;
3. Patients < 60 years of age presenting an amenorrhea of more than 12 months and
follicle stimulating hormone (FSH) and plasma estradiol levels within the
postmenopausal range as assessed by the local laboratory in the absence of
chemotherapy, tamoxifen, tolimifene, or ovarian castration in the past 1 year,
and no oral contraceptives, hormone replacement therapy, or
gonadotropin-releasing hormone agonist or antagonist;
4. Patients < 60 years of age who are taking either tamoxifen or tolomifene with
two consecutive FSH and estradiol levels in the postmenopausal range.
5. Or premenopausal or perimenopausal female subjects but must be willing to
receive and maintain an approved luteinizing hormone-releasing hormone(LHRH)
agonist during the study treatment period (LHRH agonist treatment initiated 28
days prior to the first study drug treatment);
6. Previous therapy failed or intolerable, or standard therapy not available:
Part A：Previous therapy failed or intolerable, or standard therapy not available；
Prat B/C：Patients should have received at least 1 line endocrinotherapy, or received
no more than 1-line systematic chemotherapy for advanced/metastatic disease, no more
than 1 target therapy.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. At least one measurable lesion according to RECISTv1.1 criteria.
9. Life expectancy ≥ 12 weeks.
10. Adequate organ and bone marrow function (no use of hematopoietic stimulating factor,
no blood transfusion or human albumin within 7 days prior to screening):
1. Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count
(PLT) ≥100×109/L; Hemoglobin (HGB) ≥ 90 g/L;
2. Liver function: Serum Total bilirubin (TBIL) ≤ 1.5 Upper limit of normal value
(ULN); Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤ 3×ULN
in subjects without liver metastasis; ALT or AST≤ 5×ULN with liver metastasis;
3. Renal function: Serum creatinine ≤ 1.5×ULN or estimated creatinine clearance
(CLcr) ≥ 60 mL/min as calculated using Cockcroft-Gault formula;
4. Coagulation function: Activated Partial thromboplastin Time (APTT) and
international normalized ratio (INR) ≤ 1.5×ULN (or within target range if on
anticoagulation therapy);
5. Cardiac function: Echocardiography (ECHO) shows left ventricular ejection
fraction (LVEF) > 50%.
11. Women of childbearing potential must have a negative serum pregnancy test within 7
days prior to the first dose. Female patients of childbearing potential must agree
to use effective methods of contraception from the time of signature of informed
consent, throughout the study and for 6 months after the last dose of the
investigational product, like double barrier methods, condoms, oral or injectable
contraceptives, intrauterine devices, etc. All female subjects will be considered to
be of childbearing potential unless they are postmenopausal, postmenopausal, or
sterilized (hysterectomy, tubal resection).
Exclusion Criteria:
-
1. Documented medical history or ongoing gastrointestinal disease (Including
difficulty in swallowing capsules, Crohn's disease, ulcerative colitis, or
short bowel syndrome) or other malabsorption that may affect the absorption of
oral study drug.
2. Participated in other clinical trials of investigational drugs or
investigational devices within 4 weeks before the first medication; or received
chemotherapy, targeted therapy, immunotherapy and clinical trial medication and
other anti-tumor treatment within 4 weeks, or received radiotherapy, endocrine
drugs or Chinese traditional medicines with anti-tumor indications 2 weeks
prior to the first dose.
3. The toxicity of previous anti-tumor treatment has not recovered to grade 0 or 1
(except for alopecia, chemotherapy-induced peripheral neurotoxicity ≤ grade 2).
4. Major surgical surgery (except biopsy) or incomplete healing of the surgical
incision within 4 weeks prior to the first study drug treatment.
5. Known other malignant tumors within 2 years before enrollment (except for
cervical carcinoma insitu, superficial noninvasive bladder tumors, breast
ductal carcinoma in situ, prostatic intraepithelial neoplasia without evidence
of prostate cancer, or curatively treated Stage I nonmelanoma skin cancer); 6.
unstable or syptomlor progressal Central nervous system brain metastasis ; 7.
Previous history of interstitial lung disease, drug-induced interstitial lung
disease, symptomatic interstitial lung disease or any evidence of active
pneumonia on chest CT scan within 4 weeks prior to the first study drug
treatment; 8. Known to interfere with the test requirements of mental illness
or drug abuse disease; 9. History of human immunodeficiency virus HIV
infection； 10. Active bacterial or fungal infection requiring systemic
treatment within 14 days prior to the first study drug treatment.
11. Subjects with known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection with abnormal liver function (Absence of infection was defined as
HBsAg negative, HBV DNA negative and HCV antibody negative), except to:
Subjects who test positive for HBsAg or HBsAb during the screening period may
be enrolled if the PCR test result for HCV-RNA is < 500 IU/ml (2000 copies/mL),
but receive antiviral treatment according to the investigator's assessment and
undergo PCR for HBV-DNA during the study treatment period; Subject has a
positive test for HCV antibody at screening and can be enrolled if the PCR test
result for HCV-RNA is negative.
12. History of clinically significant cardiovascular disease, such as:
1. Symptomatic congestive heart failure according to New York Heart Association
Grades (NYHA > Grade 2);
2. Severe/unstable angina, new angina within last 3 months;
3. Myocardial ischemia and long-term use of drugs for control; according to NYHA,
grade Ⅲ-Ⅳ cardiac insufficiency;
4. Any event of acute myocardial infarction within 6 months before screening;
5. Any grade ≥ 2 supraventricular arrhythmia or ventricular arrhythmia requiring
treatment or intervention;
6. Any grade atrial fibrillation, coronary/peripheral artery bypass graft, or
cerebrovascular symptoms including transient ischemic attack;
7. QTcF (Fridericia's correction formula used) > 470 ms;
8. ECG < 50 bpm. 13. History of serious allergic reactions to the study drugs or
excipients used in the protocol.
14. Women who are pregnant or lactating. 15. Prior use of an oral selective
estrogen receptor degrader (SERD). 16. Subjects who use drugs or herbal
supplements known to be moderate/strong inhibitors or inducers of CYP3A
within 2 weeks or 5 drug half-lives (whichever is longer) prior to the
first study drug treatment.
17. Received medications which inhibits the production of stomoch acid within
2 weeks or 5 drug half-lives (whichever is longer) prior to the first dose
of study drugs.
18. Received medications which inhibits P-gp within 2 weeks or 5 drug
half-lives (whichever is longer) prior to the first dose of study drugs.
19. Patients with active or chronic corneal disease, other active eye disease
requiring ongoing treatment, or any clinically significant corneal disease
for which drug-induced keratopathy cannot be adequately monitored.
20. Other conditions that the investigator considers inappropriately for this
study.
Gender:
Female
Gender based:
Yes
Gender description:
Only female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Zhang, Doctor
Phone:
18017312991
Email:
Syner2000@163.com
Start date:
September 12, 2023
Completion date:
February 2026
Lead sponsor:
Agency:
Forward Pharmaceuticals Co., Ltd.
Agency class:
Industry
Source:
Forward Pharmaceuticals Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06064812
