Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer

NCT05712941 | Withdrawn Phase 3 DMC FDA Drug

• 3 other identifiers: EQ132-303GOG-3075ENGOT-EN17
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blinded, placebo-controlled Phase 3 clinical trial to compare the combination of lerociclib (administered at 150 mg twice a day (BID) with letrozole (administered at 2.5 mg once a day (QD) to that of placebo with letrozole (2.5 mg QD) in female participants with Grade 1 or Grade 2 (ie, low-grade histology) endometrioid endometrial cancer (EC) and advanced/metastatic or recurrent disease. The study population will consist of female participants with endometrioid EC who are treatment-naïve in the advanced/metastatic setting (ie, the first-line \[1L\] population). Participants may have received prior adjuvant chemotherapy/chemoradiation for localized disease if the adjuvant therapy was administered ≥ 6 months prior. All participants must also be naïve to prior endocrine therapy for EC, and confirmed as medically postmenopausal to be eligible. The study will comprise a Screening Period of up to 28 days in duration; a Study Treatment Phase; a Safety Follow-up Period spanning the time of study treatment discontinuation-including discontinuation due to confirmed disease progression, as applicable-through 28 days after the participant's last dose of any study intervention or the start of subsequent anticancer therapy (whichever occurs first); and a Survival Follow-up Period that will continue until the participant's death or until at least 50% of all study participants have died (whichever occurs first). While receiving their randomized assigned study treatment, participants will undergo imaging assessments via computed tomography (CT) of the chest/abdomen/pelvis with contrast- or, if CT is medically contraindicated (eg, due to iodine allergy), via magnetic resonance imaging (MRI) with gadolinium-every 8 weeks for the first 12 months and then every 12 weeks thereafter.

Conditions

Endometrial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the time from randomization until the date of document disease progression (per RECIST v1.1) or death

  Through study completion, an average of 27 months

Secondary Outcomes (4)

• Overall Survival (OS)

  Through study completion, an average of 27 months

• Progression Free Survival (PFS) by Investigator

  Through study completion, an average of 27 months

• Patient Reported Outcomes/Quality of Life

  Through study completion, an average of 27 months

• Safety/Tolerability

  Through study completion, an average of 27 months

Study Arms (2)

Letrozole 2.5mg by mouth once a day (QD) + Lerociclib 150mg by mouth twice a day (BID)

EXPERIMENTAL

Drug: Lerociclib; Drug: Letrozole 2.5mg

Letrozole 2.5mg by mouth once a day (QD) + Placebo

PLACEBO COMPARATOR

Drug: Letrozole 2.5mg; Drug: Placebo

Interventions

Lerociclib DRUG

All participants should be treated according to the best-current-practice guidelines and standard of care within each institution or country where the study is conducted. Participants will be randomized to receive either lerociclib (administered at 150 mg twice a day (BID) in combination with letrozole (administered at 2.5 mg once a day (QD), or placebo administered in combination with letrozole (2.5 mg QD). Participants will also be stratified, using interactive response technology (IRT), by the following randomization strata: * Endometrial Cancer (EC) tumor staging (Federation Internationale de Gynecologie et d'Obstetrique \[FIGO\] Stage III versus FIGO Stage IV versus recurrent) * EC tumor grade (Grade 1 versus Grade 2) * Geographic location (US versus Europe versus Rest of World)

Letrozole 2.5mg by mouth once a day (QD) + Lerociclib 150mg by mouth twice a day (BID)

Letrozole 2.5mg DRUG

All participants should be treated according to the best-current-practice guidelines and standard of care within each institution or country where the study is conducted. Participants will be randomized to receive either lerociclib (administered at 150 mg twice daily (BID) in combination with letrozole (administered at 2.5 mg once a day (QD), or placebo administered in combination with letrozole (2.5 mg QD). Participants will also be stratified, using interactive response technology (IRT), by the following randomization strata: * Endometrial Cancer (EC) tumor staging (Federation Internationale de Gynecologie et d'Obstetrique \[FIGO\] Stage III versus FIGO Stage IV versus recurrent) * EC tumor grade (Grade 1 versus Grade 2) * Geographic location (US versus Europe versus Rest of World)

Letrozole 2.5mg by mouth once a day (QD) + Lerociclib 150mg by mouth twice a day (BID); Letrozole 2.5mg by mouth once a day (QD) + Placebo

Placebo DRUG

All participants should be treated according to the best-current-practice guidelines and standard of care within each institution or country where the study is conducted. Participants will be randomized to receive either lerociclib (administered at 150 mg twice day (BID) in combination with letrozole (administered at 2.5 mg once a day (QD), or placebo administered in combination with letrozole (2.5 mg QD). Participants will also be stratified, using interactive response technology (IRT), by the following randomization strata: * Endometrial Cancer (EC) tumor staging (Federation Internationale de Gynecologie et d'Obstetrique \[FIGO\] Stage III versus FIGO Stage IV versus recurrent) * EC tumor grade (Grade 1 versus Grade 2) * Geographic location (US versus Europe versus Rest of World)

Letrozole 2.5mg by mouth once a day (QD) + Placebo

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if they meet all of the following criteria, as applicable:
• Applicable to All Participants
• Is capable of providing signed informed consent as described in Section 10.1.1, which includes compliance with the requirements and restrictions listed in the study informed consent form (ICF) and in this protocol.
• Is at least 18 years of age, or the legal age of consent in the jurisdiction in which the study is taking place, at the time of providing signed informed consent.
• Has confirmed Grade 1 or Grade 2 (ie, low-grade histology) endometrioid endometrial adenocarcinoma.
• Note: Mixed tumor histology is permitted, provided that the non-endometrioid component is \< 5%.
• Is treatment-naïve for Endometrial Cancer (EC) in the advanced/metastatic setting.
• Is naïve to prior endocrine therapy for EC.
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Has adequate organ function, as defined by all of the following:
• Absolute neutrophil count ≥ 1.5 × 10\^9/L
• Platelets ≥ 100 × 10\^9/L
• Hemoglobin ≥ 8.0 g/dL
• International Normalized Ratio (INR) ≤ 1.5, unless participant is receiving chronic anti-coagulation therapy as noted below.
• Note: Therapeutic INR is higher in individuals on chronic anti-coagulation treatment. Any such participant whose INR exceeds 1.5 may be considered eligible per Investigator judgment if otherwise meeting the study entry criteria.

You may not qualify if:

• Participants are excluded from this study if they meet any of the following criteria, as applicable:
• Applicable to All Participants
• Tumor histology includes any non-endometrioid component of ≥ 5%.
• Has EC that meets either of the following criteria:
• Is amenable to curative intent therapy (ie, surgery, radiation, etc).
• Was previously treated with systemic therapy (eg, chemotherapy) in the advanced/metastatic setting.
• Note: Prior adjuvant chemotherapy is allowed, provided that it was completed ≥ 6 months before study enrollment.
• Has leptomeningeal carcinomatosis or central nervous system (CNS) metastases, unless the participant meets all of the following criteria:
• Has completed prior therapy for CNS tumor at least 4 weeks before initiating study treatment.
• Has stable CNS tumor at Screening.
• Is not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
• Is known to exhibit loss of retinoblastoma protein (Rb) on genetic testing of tumor tissue, if identified per one of the following methods prior to enrollment (note that Rb testing is not an enrollment requirement):
• PCR
• Next-generation sequencing
• Peripheral blood testing

Sponsors & Collaborators

• EQRx International, Inc.: lead
• GOG Foundation: collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: February 6, 2023
• Study Start: April 18, 2023
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2025
• Last Updated: November 3, 2023

Record last verified: 2023-11