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Letrozole

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Orange

Phase 1: Initiating at 160mg per day of narazaciclib, patients will receive escalating doses of narazaciclib (oral tablets/once daily) in combination with 2.5mg of letrozole (oral tablet/once daily).

Phase 2: All patients will receive the recommended phase 2 dose (RP2D) of the combination of narazaciclib (oral tablets) and letrozole (oral tablet/QD)

Orange tablets, each containing 40 mg or 120 mg of narazaciclib as narazaciclib monolactate

Narazaciclib

Letrozole 2.5mg

Victor Moyo, MD

Stacey Kimbell, RN

Julie Klinker, RN

Joseph Buscema, MD

Brianna Lenox

Timothy G Larson, MD

Bhavana Pothuri, MD

Jeanne Schaffer, RN, BSN

Nichole Fisher, RN, BSN

Charles K Anderson, MD

Fiona Davidson

Lisa Johnson

W. Jeff Edenfield, MD

Christine Terraciano

Noelle G Cloven, MD

Nori Sullivan, RN, BSN

This study will assess the safety and efficacy of increasing doses of narazaciclib (ON 123300) in combination with the standard daily dose (2.5mg) of letrozole in patients with Recurrent Metastatic Low-grade Endometrioid Endometrial Cancer and other Gynecologic Malignancies.

This is a phase 1/2a, open-label, multicenter study to evaluate the safety, tolerability and efficacy of escalating doses of narazaciclib (ON 123300) in combination with letrozole for patients with recurrent metastatic low-grade endometrioid endometrial cancer and other Gynecologic Malignancies. Pharmacokinetics and pharmacodynamics will also be assessed.

In Phase 1, eligible patients will be enrolled to escalating dose cohorts. Cohorts will receive escalating doses of oral narazaciclib starting at 160 mg orally, once daily, in combination with letrozole 2.5 mg orally, once daily, in 28-day cycles in a typical 3 + 3 design. The dose of narazaciclib will be increased in 40 mg/day increments from cohort to cohort until the maximum tolerated dose (MTD) and/or the minimal biologically effective dose (MBED) of narazaciclib orally, once daily, in combination with letrozole 2.5 mg orally, once daily, is reached and the RP2D of the combination is established. Three to 6 patients will be enrolled per dose cohort in phase 1.

In Phase 2a, narazaciclib and letrozole at the RP2D established in Phase 1 will be administered to approximately 30 eligible patients with documented recurrent metastatic LGEEC for 28-day cycles. Treatment will continue until disease progression, patient withdrawal, or unacceptable drug-related toxicity.

Phase 1: 3+3 dose escalation Phase2: Expansion cohort

Study of Narazaciclib (ON 123300) Plus Letrozole in Endometrial Cancer and Other Gynecologic Malignancies

A Multi-center Phase 1/2a Study of Narazaciclib (ON 123300) in Combination With Letrozole as Therapy for the Treatment of Recurrent Metastatic Endometrial Cancer and Other Gynecologic Malignancies

Highest concentration of drug measured in the PK samples

Time from dosing until collection of the PK samples with the highest drug concentration.

The area under the concentration-time curve from dosing (time 0) to time t.

Tyrosine kinase 1 (TK1) is a metabolic enzyme fundamentally involved in DNA synthesis that plays a critical role in cell proliferation

Percentage of patients experiencing TEAEs, by system organ class (SOC) and preferred term

Progression or other status determined by RECIST assessment

Time from first dose to progression by RECIST assessment. A Kaplan-Meier curve will be provided.

Percentage of patients achieving a CR by RECIST

Percentage of patients achieving a PR by RECIST

Percentage of patients maintaining SD by RECIST

Percentage of patients achieving a CR or PR by RECIST

Percentage of patients achieving a CR or PR or maintaining SD by RECIST

Time from definition of response to diagnosis of progression. A Kaplan-Meier curve will be provided.

Time from first dose until definition of response. A Kaplan-Meier curve will be provided.

Time from first dose until death from any cause. A Kaplan-Meier curve will be provided.

Spots Global Cancer Trial Database for on 123300

Every month we try and update this database with for on 123300 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 on 123300

Every month we try and update this database with for on 123300 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 on 123300 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.