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

NCT05705505 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 19-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Endometrioid Endometrial Cancer

Keywords

Narazaciclib; ON 123300; letrozole

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities (DLTs) will be tabulated and summarized by cohort

  Number of DLTs per cohort

  From First dose until end of Cycle 1 (28 days)

• Treatment-emergent adverse events (TEAEs), including DLTs will be graded by CTCAE v5.0

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

  From first dose until 30 days after final dose, up to approximately 1 year

• Phase 2 - Progression-free survival (PFS) at 24 weeks by Investigator assessment

  Progression or other status determined by RECIST assessment

  Measured from first dose until 24-weeks

Secondary Outcomes (10)

• PFS at 16 weeks by Investigator assessment

  Measured from first dose until 16-weeks

• Median PFS by Investigator assessment

  Measured from first dose until diagnosis of progression including 2 years of follow-up after discontinuation of treatment.

• Complete response (CR) rate

  From first dose until occurrence of response or progression, up to 1 year

• Partial response (PR) rate

  From first dose until occurrence of response or progression, up to 1 year

• Stable disease (SD) rate

  From first dose until occurrence of response or progression, up to 1 year

Other Outcomes (4)

• Pharmacokinetics (PK): Maximum plasma concentration of drug (Cmax)

  Samples will be collected a predose through 24 hours post dose on Days 1 and 8, then pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1

• PK: Time to reach Cmax (Tmax)

  Samples will be collected a predose through 24 hours post dose on Days 1 and 8, then pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

• PK: Area under the concentration-time curve (AUC) from time 0 to time of last quantifiable sample (AUC0-t)

  Samples will be collected a predose through 24 hours post dose on Days 1 and 8, then pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

Study Arms (1)

Escalating daily doses of narazaciclib in combination with letrozole (2.5mg day)

EXPERIMENTAL

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)

Drug: Narazaciclib; Drug: Letrozole 2.5mg

Interventions

Narazaciclib DRUG

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

Also known as: ON 123300, HX-301

Escalating daily doses of narazaciclib in combination with letrozole (2.5mg day)

Letrozole 2.5mg DRUG

Tablet

Also known as: Femara

Escalating daily doses of narazaciclib in combination with letrozole (2.5mg day)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 18 years of age, or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing informed consent form (ICF).
• Phase 1 (Dose escalation cohorts): Have confirmed endometrial or other gynecologic malignancy that is amenable for treatment with hormonal therapy and do not have other standard treatment options. (Patients with endometrioid and other types of uterine cancer as well as ovarian cancers may be enrolled at the Investigator's discretion if hormonal based therapy is considered an appropriate option for the patient).
• OR Phase 2a (Dose expansion cohort): Have confirmed low-grade (Federation of Gynaecology and Obstetrics \[FIGO\] Grade 1 or 2) endometrioid endometrial cancer (LGEEC). Mixed tumor histology is allowed if the non-endometrioid component is \<5%.
• Recurrent metastatic disease or advanced (Stage IV) disease.
• Phase 1 (Dose escalation cohorts): Patients may be enrolled regardless of prior checkpoint inhibitor therapy, at the Investigator's discretion.
• OR Phase 2a (Dose expansion cohort): Have received prior checkpoint inhibitor therapy (single agent or in combination with another anti-cancer therapy) if available for this indication and NOT contraindicated.
• Phase 1 (Dose escalation cohorts): Patients may be enrolled who have not received prior therapy for recurrent/metastatic disease, or have received any number of prior lines of therapy for recurrent/metastatic disease, at the Investigator's discretion.
• OR Phase 2a (Dose expansion cohort): Have received 1 or 2 prior lines of systemic therapy for metastatic disease. Patient has NOT received more than 2 prior lines of systemic therapy for metastatic LGEEC (including checkpoint inhibitor, hormone therapy, or chemotherapy). Prior external beam radiotherapy, brachytherapy, and/or surgery for localized disease is allowed and is not counted as a line of therapy.
• Phase 1 (Dose escalation cohorts): Have either measurable or non- measurable disease.
• OR Phase 2a (Dose expansion cohort): Have measurable disease outside the radiated field.
• Local mismatch repair (MMR) immunohistochemistry (IHC) results available (both deficient mismatch repair (dMMR) and mismatch repair protein (MMRP) deficiency (MMRp) patients are eligible, and will be documented for research purposes).
• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Tissue for estrogen/progesterone receptor status and molecular classification (paraffin embedded or fresh biopsy if unavailable).
• Have adequate organ function as indicated by the following:
• Absolute neutrophil count (ANC) ≥1.0×109/L

You may not qualify if:

• Phase 1 (Dose escalation cohorts): Cancer other than endometrial or other gynecologic malignancy.
• Have received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the past.
• Have any significant medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the Investigator, would prevent the patient from participating in the study or present an unacceptable risk to the patient.
• Are at risk for Torsades de pointes (TdP): Patients who have a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>470 msec) using Fredericia's QT correction formula, or who have a history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or who are currently taking medications that prolong the QT/QTc interval.
• Have uncontrolled intercurrent or significant medical illness, serious underlying medical condition, abnormal laboratory finding, or psychiatric illness/social situation that might, in the Investigator's or the Sponsor's judgment, prevent the participant from receiving study treatment or being followed in this study, or otherwise renders the participant inappropriate for the study, including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, and psychiatric illness/social situations that limit participation compliance with study procedures and requirements.
• Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP)2C8 and CYP3A4.
• Have a recent history of venous thromboembolic events, defined as event occurring \<6 months prior to screening and also currently on therapy, known underlying hypercoagulability, or a major thromboembolic event within the past 2 years.
• Have baseline Grade ≥2 diarrhea.
• Have Grade ≥3 hypercalcemia (corrected serum calcium \>12.5 mg/dL).
• Are pregnant or nursing mothers.
• Have had major surgery within 14 days prior to screening to allow for postoperative healing of the surgical wound and site(s).
• Have received recent (within 28 days prior to screening) live attenuated vaccines.
• Have active infection, including bacterial or fungal infections or active viral infection or viral load, including any human immunodeficiency virus (HIV), or hepatitis B virus (HBV), hepatitis C virus (HCV), or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19).
• Currently have or have been treated in the past 2 years, for any other cancer or malignancy, except:
• Non-melanoma skin cancer, including basal cell carcinoma of the skin

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (8)

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711, United States

RECRUITING

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, 55404, United States

RECRUITING

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

NYU Langone

New York, New York, 10016, United States

RECRUITING

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

RECRUITING

Greenville Health System, Institute for Oncology Clinical Research

Greenville, South Carolina, 29605, United States

RECRUITING

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, 76104, United States

RECRUITING

MeSH Terms

Interventions

ON123300; Letrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Victor Moyo, MD

  Onconova Therapeutics

  STUDY CHAIR

Central Study Contacts

Victor Moyo, MD

CONTACT

484 535 1402; vmoyo@onconova.us

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: January 30, 2023
• Study Start: March 29, 2023
• Primary Completion: January 1, 2026
• Study Completion: February 1, 2026
• Last Updated: December 12, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)