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Palbociclib

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.

The dose expansion study will be conducted in approximately 12 eligible subjects diagnosed with ER+/HER2- unresectable locally advanced or metastatic breast cancer, to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of FWD1802 in combination with palbocilib.

The starting dose level for Part B study will be determined by SMC based on safety data (including the AE rate of non-DLT) , PK, PD and preliminary efficacy in Part A. Every treatment cycle consists of 28 days.

In brief, based on the available data obtained from Part A, 1 to 2 dose levels may be selected as the recommended dose levels (RDs) to evaluate FWD1802 in combination with palbocilib in these patients.

Part C (Dose Expansion of FWD1802 as a Monotherapy) can be conducted in parallel with Part A provided that the following two conditions are met:

1. The starting dose of Part C study should be lower than the dose of monotherapy RP2D or the dose that has been explored and confirmed as safe for monotherapy.
2. The SMC will review all available PK, PD, safety, tolerability and efficacy data for Part A study and decide whether the study may proceed to Part C portions.

The dose expansion study will be conducted in approximately 60 eligible subjects diagnosed with ER+/HER2-/ESR1 mutation unresectable locally advanced or metastatic BC, to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of FWD1802 Tablet at the recommended 1\~2 dose level(s) for expansion.

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.

FWD1802

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.

palbocilib

Huan Liu

Jian Zhang, Doctor

Jian Zhang

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.

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.

A Phase I Clinical Trial of FWD1802 in Patients With ER+/HER2- BC.

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 correlation between ER target inhibition by using \[18F\]-fluorestradiol (FES) PET/CT and efficacy.

Progression free survival (PFS) and Overall survival (OS) Other potential biomarker as needed.

Incidence of DLT in the MTD evaluation period, adverse events, treatment emergent adverse event (TEAE), serious adverse event (SAE), their relationship with the investigational product and respective severity. Changes in vital signs, ECOG score, ECG, physical examination, and laboratory tests before and after treatment, and the use of concomitant medication.

Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC0-t)

The area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)

Minimum concentration at steady state (Cmin_ss)

Maximum concentration at steady state (Cmax_ss)

Average concentration at steady state (Cave_ss)

accumulation ratio (AR) based on Cmax and AUCtau_ss

Tumor response assessments by the corresponding criteria by RECIST v1.1 to assess Objective response rate (ORR)

Spots Global Cancer Trial Database for palbocilib

Every month we try and update this database with for palbocilib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for palbocilib

Every month we try and update this database with for palbocilib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for palbocilib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.