A Phase I/II Study of FWD1802 in Patients With ER+/HER2- Advanced BC.

NCT06064812 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: FWD1802-001C
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 22

Brief Summary

A Phase I/II, Open-label study to assess the safety, tolerability, pharmacokinetic, and antitumor efficacy of FWD1802 monotherapy in patients with ER+/HER2- unresectable locally advanced or metastatic breast cancer. This clinical trial aims to explore the role of FWD1802 in the ER+/HER2- advanced breast cancer patient population. The primary objectives are to address the following questions: Phase I Study: Determine the Recommended Phase II Dose (RP2D) and/or Maximum Tolerated Dose (MTD) of FWD1802 in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. Phase II Study: To evaluate the efficacy of FWD1802 at the RP2D in patients with ESR1-mutated ER-positive/HER2-negative locally advanced or metastatic breast cancer, using objective response rate (ORR) as the efficacy endpoint.

Conditions

Metastatic Breast Cancer; Locally Advanced Breast Cancer; Breast Cancer Stage IV; ER+/HER2- Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I Study

  Dose-Limiting Toxicity (DLT) Maximum Tolerated Dose (MTD) Recommended Phase II Dose (RP2D)

  Approximately 2 years

• Phase II Study

  Objective Response Rate (ORR) as assessed by the investigator per RECIST v1.1

  Approximately 2 years

Secondary Outcomes (2)

• Phase I Study

  Approximately 2 years]

• Phase II Study

  Approximately 2 years

Other Outcomes (1)

• The sponsor will determine whether and when to conduct exploratory investigations based on the study progress.

  Approximately 2 years

Study Arms (3)

Phase I Study Part A: Dose Escalation.

EXPERIMENTAL

Part A study will be conducted in subjects diagnosed with ER+/HER2- unresectable locally advanced or metastatic breast cancer. A maximum of 27 subjects will be enrolled. They will be sequentially allocated to 5 planned dose cohorts: 25 mg, 75 mg, 150 mg, 300 mg and 450 mg. Subjects enrolled will be orally administered a single dose of FWD1802 Tablet on C0D1, followed by a 3-day observation period. Starting on C1D1, FWD1802 Tablet will be orally administered continuously QD for 28 consecutive days of each cycle. The DLT observation period is set as 32 days(C0D1-C1D28). The second cycle and subsequent cycles will last for 28 days per cycle. The patients will continue to receive the study treatment until PD, death, unacceptable toxicity, withdrawal of informed consent, or other reasons to discontinue study treatment occurs, whichever comes first.

Drug: FWD1802

Phase I Study Part B - Dose Expansion.

EXPERIMENTAL

Part B will be conducted based on the dose-escalation results from Part A (comprehensive safety, PK, PD, and other data), selecting 2 to 4 dose cohorts for further exploration of the PK characteristics and RP2D of FWD1802. Each dose cohort will be expanded to include a maximum of 10 subjects (this total includes subjects from the corresponding dose cohort in Part A). The doses selected for Part B must be within the dose levels already explored and confirmed as safe to ensure that all doses in Part B fall within a known safety range. The SMC will decide on the 2 to 4 doses for expansion, which may include doses already confirmed as safe in Part A or new doses within the established safe range. The timing for initiating Part B will be jointly determined by the SMC and the sponsor based on the information already obtained from Part A. Part B may commence concurrently with the dose-escalation phase. The 2 to 4 dose cohorts in Part B may be conducted simultaneously or sequentially.

Drug: FWD1802

Phase II Study - Dose Expansion in ER+/HER2- Subjects with ESR1 Mutations.

EXPERIMENTAL

The dose expansion study will be conducted in approximately 60 subjects diagnosed with ER+/HER2- locally advanced or metastatic breast cancer harboring ESR1 mutations, to evaluate the efficacy, safety and PK of FWD1802 at the recommended 1 to 2 dose level(s). The specific number of subjects, dosage(s), and dosing regimen in the dose expansion study will be comprehensively determined by the SMC based on the results from the Phase I, Part A study. Subjects will undergo ctDNA testing before treatment initiation, on Cycle 1 Day 15 (C1D15), on Cycle 2 Day 1 (C2D1), after disease progression, and when deemed necessary based on the subject's therapeutic response, to determine the baseline mutation sites, types, and frequencies of ESR1 and/or other breast cancer-related genes.

Drug: FWD1802

Interventions

FWD1802 DRUG

Eligible subjects will receive FWD1802 treatment according to their assigned dose cohort. Dose Escalation Phase: This phase is divided into a Single-Agent Lead-in Period (C0) and a Multiple-Dosing Period (C1). During the single-agent lead-in period, subjects will receive one dose on Day 1, followed by a 6-day dosing pause. In the multiple-dosing period, subjects will be administered FWD1802 once daily. Dose Expansion Phase: Subjects will receive FWD1802 once daily. Each 4-week period constitutes one treatment cycle. Treatment will continue for up to 2 years or until one of the following events occurs (whichever comes first): disease progression, intolerable toxicity, withdrawal of informed consent, loss to follow-up, initiation of new anti-cancer therapy, or death. Patients who remain in the study at the end of the 2-year treatment period and continue to derive clinical benefit may, upon agreement between the investigator and the sponsor, have the option to continue treatment.

Phase I Study Part A: Dose Escalation.; Phase I Study Part B - Dose Expansion.; Phase II Study - Dose Expansion in ER+/HER2- Subjects with ESR1 Mutations.

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be eligible for enrollment in this clinical study:
• Voluntarily participate in the clinical trial and sign the informed consent form.
• Female, aged ≥18 years.
• Able to provide blood samples for central laboratory testing of ESR1 mutation status and other biomarker assessments. Phase I Study: ESR1 mutation status will be tested retrospectively. Phase II Study: Only subjects with confirmed ESR1 mutations will be enrolled (see Appendix 5 for details).
• Histologically or cytologically confirmed locally advanced or metastatic breast cancer that is ER-positive and HER2-negative.
• Criteria for ER positivity: Immunohistochemistry staining shows nuclear staining in ≥10% of tumor cells.
• Criteria for HER2 negativity: Immunohistochemistry staining intensity is 0 or 1+; if the intensity is 2+, it must be confirmed negative by in situ hybridization.
• Confirmed in menopause and not caused by ovarian function suppression drugs, must meet one of the following criteria:
• Previous bilateral oophorectomy. Age ≥ 60 years.
• Age \< 60 years (subdivided into the following conditions):
• Never received chemotherapy, ovarian function inhibitors, or SERM drugs (tamoxifen, toremifene), with amenorrhea ≥12 months, and E2 and FSH levels in the postmenopausal range.
• Received chemotherapy resulting in chemotherapy-induced amenorrhea ≥12 months, with E2 and FSH levels in the postmenopausal range.
• Using SERM drugs (tamoxifen, toremifene), with E2 and FSH levels in the postmenopausal range.
• Premenopausal or perimenopausal female subjects must agree to receive and maintain treatment with ovarian function suppression (LHRH agonists) during the study treatment period (ovarian function suppression treatment must be initiated at least 14 days before the first dose of study drug).
• Prior treatment history must meet the following requirements:

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Leptomeningeal metastases, carcinomatous meningitis, spinal cord compression, or symptomatic or clinically unstable central nervous system (CNS) metastases.
• History of ongoing gastrointestinal diseases or other malabsorptive conditions that may impact the absorption of orally administered study drugs, including but not limited to:
• Inability to swallow oral medications.
• Requirement for intravenous nutrition.
• Prior surgery affecting absorption, including total/partial gastrectomy.
• Crohn's disease, ulcerative colitis.
• Treatment for active peptic ulcer disease within 6 months prior to the first dose.
• Malabsorption syndrome, or uncontrolled nausea, vomiting, or diarrhea.
• Patients with symptomatic visceral metastases, or those with clinically significant and unstable pleural, peritoneal, pericardial effusions, or pulmonary lymphangitic carcinomatosis. Patients who have received intracavitary infusion therapy or drainage/paracentesis may be enrolled 14 days or more after the effusion has stabilized. Other conditions deemed by the investigator as unsuitable for endocrine therapy.
• Prior treatments do not meet the following washout periods:
• Use of other investigational drugs or devices within 4 weeks prior to the first dose.
• Treatment with CDK4/6 inhibitors or mTOR inhibitors within 2 weeks, or other targeted therapies, chemotherapy, or immunotherapy within 4 weeks prior to the first dose.
• Treatment with mitomycin or nitrosoureas within 6 weeks prior to the first dose.
• Use of drugs or herbal supplements known to be moderate/strong inhibitors or inducers of CYP3A4 within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose (see Appendix 4).

Sponsors & Collaborators

• Forward Pharmaceuticals Co., Ltd.: lead

Study Sites (22)

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Huizhou First Hospital

Huizhou, Guangdong, China

RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

RECRUITING

The First Affiliated Hospital of Henan University of Science & Technology

Luoyang, Henan, China

RECRUITING

Xinxiang Central Hospital

Xinxiang, Henan, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

NOT YET RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, China

NOT YET RECRUITING

The Central Hospital of Yongzhou

Yongzhou, Hunan, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, China

RECRUITING

The First Hospital of Jilin University

Changchun, Jilin, China

RECRUITING

First Affiliated Hospital of China Medical University

Shenyang, Liaoning, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, China

RECRUITING

The second people's hospital of Yibin

Yibin, Sichuan, China

RECRUITING

Tianjin Medical University Cancer institute & Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

Sir Run Run Shaw Hospital,affiliated with Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jian Zhang

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Limin Yin

CONTACT

18520159114; yinlm@forward-pharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: October 3, 2023
• Study Start: September 12, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (22)