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Imlunestrant/Abemaciclib/Selinexor in Ovarian and Endometrial

ConditionsLow Grade Ovarian Serous AdenocarcinomaEndometrial Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorDana-Farber Cancer Institute

About this trial

This is a phase 2, interventional treatment trial evaluating imlunestrant, abemaciclib, and selinexor in two separate patient cohorts: low grade serous ovarian cancer and endometrioid endometrial cancer. The study is non-randomized and open-label. Treatment is administered in the outpatient setting, with a 14-day Cycle 0 followed by 28-day treatment cycles.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

For Cohort 1A: Participants must have histologically confirmed diagnosis of low-grade serous carcinoma of ovary, fallopian tube or peritoneum that is recurrent or metastatic and/or resistant to standard therapies; original diagnosis of de novo low-grade serous carcinoma or original diagnosis of serous borderline tumor with subsequent diagnosis of low-grade serous carcinoma are allowed. Participants whose tumors contain both low-grade serous carcinoma and high-grade serous carcinoma are not eligible.

For Cohort 1B: Participants must have cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies. Participants must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component.

For both cohorts, tumor must be TP53 wild-type as determined by immunohistochemistry (IHC) or via CLIA-certified targeted NGS.

Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

Disqualifiers

Participants who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of protocol therapy. Participants who have had hormonal therapy within 2 weeks of the first dose of protocol therapy. Participants who have received experimental treatment within the last 28 days or 5 half-lives, whichever is shorter, prior to initiation of study therapy

Patients who had wide-field radiotherapy ≤4 weeks (defined as involving ≥25% of the bone marrow), or limited field radiation for palliation ≤1 week prior to initiation of study therapy.

Participants who have not recovered from adverse events due to prior anti-cancer therapy administration (e.g., have residual toxicities > Grade 1) with the exception of alopecia. Patients with stable Grade 2 neuropathy that does not affect ability to perform ADLs or who have clinically recovered from prior adverse events but remain on appropriate medical management (e.g. therapeutic anticoagulation for thromboembolic events; antihypertensives for hypertension) may also be considered eligible for the study after discussion with the sponsor-investigator). Patients with residual Grade 2 anemia who meet the marrow function criteria as defined in 3.1.8 will also be considered eligible. Participants with prior Grade 2 endocrine toxicities (hypothyroidism, adrenal insufficiency, etc) from checkpoint inhibitor therapy that are well managed with hormone supplementation are allowed.

Participants who are receiving any other investigational agents for this condition.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Imlunestrant

    Drug

    Oral study drug Taken once per day

  • Abemaciclib

    Drug

    Oral study drug Taken twice per day

  • Selinexor

    Drug

    Oral study drug Taken once per week

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: 1A - Low grade serous ovarian cancer cohortExperimental treatment 3 interventions
Group B: 1B - Endometrioid endometrial cancer cohortExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Objective Response Rate (ORR)

ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Time frame
Treatment duration depends on individual response, evidence of disease progression, and treatment tolerance. On average, up to 1 year.

Secondary outcomes

1

Progression-Free Survival at 6 Months (PFS6)

PFS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. PFS is defined as the time from the date of the first study dose to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

Time frame
6 months
2

Median Overall Survival (OS)

OS based on Kaplan-Meier method is defined as the time from first study dose to death due to any cause, or censored at date last known alive.

Time frame
Survival status is assessed every 6 months for up to 3 years following the end-of-treatment assessment, or until death, whichever occurs first. Treatment duration depends on individual response, disease progression, and treatment tolerance.
3

Median Progression-Free Survival (PFS)

PFS based on Kaplan-Meier method is defined as the time from the date of the first study dose to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

Time frame
Tumor assessments are performed every 8 weeks during treatment. Treatment duration depends on individual response, evidence of disease progression, and treatment tolerance. On average, up to 3 years.
4

Treatment-Related Adverse Events (TRAE) Rate

TRAE rate is defined as the proportion of participants who experience at least one adverse event considered to be possibly, probably, or definitely related to study treatment.

Time frame
AE assessments are performed at all study visits during treatment, and adverse events are collected through 30 days after the end of treatment. Treatment duration depends on individual response. On average, up to 1 year.

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Dana-Farber Cancer Institute

Lead sponsor

Eli Lilly and Company

Collaborator

Karyopharm Therapeutics Inc

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: