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Low Grade Ovarian Serous AdenocarcinomaPhase 2SIERRANCT07832227

Imlunestrant/Abemaciclib/Selinexor in Ovarian and Endometrial

A Phase 2 study testing Imlunestrant, Abemaciclib and Selinexor in people with Low Grade Ovarian Serous Adenocarcinoma and Endometrial Cancer, run by Dana-Farber Cancer Institute.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Imlunestrant, Abemaciclib and Selinexor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
No sites listed yet
Study dates
1 Dec 2026to 1 Aug 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • For Cohort 1A: After the safety lead-in, participants must have biopsiable disease in a lesion that is not being utilized as the target lesion for RECIST assessment and willing to undergo two on-treatment biopsies.
  • (NOTE: If a patient is included in the safety lead-in, the presence of biopsiable disease and willingness to undergo serial on-treatment biopsies is not required. After the safety lead-in, this requirement will remain for 14 participants, after which the biopsy requirement will no longer be mandatory for enrollment.
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix A)
  • Age ≥ 18 years
  • Participants must have normal organ and bone marrow function within 14 days before starting protocol therapy as defined below:
  • Hematologic
  • ANC ≥1.5 × 10^9/L
  • Platelets ≥100 × 10^9/L Patients must have at least a 1-week interval from the last platelet transfusion prior to the screening platelet assessment.
  • Hemoglobin
  • ≥9 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
  • Hepatic
  • Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
  • ALT and AST ≤3 × ULN or ≤5 × ULN if liver metastases
  • Creatinine
  • ≤ 1.5 × institutional ULN, OR ≥ 60 mL/min/1.73 m2 per the CKD-EPI formula for participants with creatinine levels above 1.5 x institutional ULN.
  • The CKD-EPI formula is calculated as:
  • GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 ×
  • Creatinine clearance 0.993Age × 1.018 [if female] × 1.159 [if black]
  • where: Scr is serum creatinine in mg/dL, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1. Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to swallow and retain oral medications.
  • Participants can have received an unlimited number of prior therapies.
  • Participants must have previously received hormonal therapy of any type, including, but not limited to, aromatase inhibitors, tamoxifen or other selective estrogen receptor modulators, progestin analogues, selective estrogen receptor degraders (such as fulvestrant or elacestrant), agents targeting the GnRH-LH-FSH pathway (such as leuprolide acetate or goserelin acetate). Prior imlunestrant is allowed.
  • Participants must be willing to release archival tissue if available. Please see section 9.1 and the laboratory manual for tissue requirements.
  • The effects of the study agents on the developing human fetus are unknown. Female patients of childbearing potential must have a negative serum pregnancy test at screening. Furthermore, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
  • Female participants must agree not to donate egg during the study treatment period and for 90 days following last dose of study treatment.
  • HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. However, participants who are on antiretroviral therapy that includes strong inhibitors or inducers of CYP3A4 are not eligible, given the potential for interaction with abemaciclib.
  • Participants with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression. Participants with new or progressive brain metastases (active brain metastases) are eligible only if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first two cycles of therapy. Participants with known leptomeningeal disease are not eligible.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Who cannot join

  • 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.
  • Participants may not have had prior receipt of abemaciclib or any CDK4/6 inhibitor.
  • Participants may not have had prior receipt of selinexor or any XPO1 inhibitor.
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  • Participants with an inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by NCCN Clinical Practice Guidelines in Oncology (NCCN CPGO) for antiemesis and anorexia/cachexia.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to imlunestrant, abemaciclib and selinexor.
  • Participants with active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
  • Participants who at the time of study enrollment are known to require concomitant therapy with strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior to the first dose of study medication.
  • Pregnant women are excluded from this study because of the apoptotic and cytostatic effects of imlunestrant, abemaciclib and selinexor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with the study drugs.
  • Any gastrointestinal dysfunctions that could interfere with the absorption of study drugs (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea).
  • Major injuries or surgery within 28 days prior to starting study treatment and/or planned major surgery during the on-treatment study period.
  • Hospitalization for any reason within 14 days of starting study treatment.
  • The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease/pneumonitis, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, cannabis, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, and ginseng). Participants should stop herbal medications at least 7 days prior to starting study treatment.
  • Participants with personal history of any of the following conditions, in the judgment of the investigator: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Panagiotis Konstantinopoulos, MD, PhD contact

6176322334

Panagiotis_Konstantinopoulos@dfci.harvard.edu

About this study

Official title: A Phase II Trial of Imlunestrant/Abemaciclib/Selinexor in Low Grade Serous Ovarian Cancer and in Endometrioid Endometrial Cancer

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.

Read the detailed description

This DF/HCC PI-sponsored interventional phase 2 trial studies the combination of imlunestrant, abemaciclib, and selinexor in gynecologic cancer cohorts defined by disease type. Baseline evaluations are performed within 14 days before protocol therapy starts, while informed consent and baseline imaging must be completed within 30 days before treatment start. Protocol assessments include physical exams, vital signs, ECOG performance status, CBC, serum chemistries, EKGs, radiologic evaluations, tissue collection, and peripheral blood research collection; Cohort 1A also includes CA-125 testing and research biopsy procedures. Radiologic evaluations are performed every 8 weeks after initiation of Cycle 1, and follow-up continues after treatment discontinuation, including survival follow-up every 6 months.

Being tested
Imlunestrant, Abemaciclib, Selinexor
Keywords
Low grade serous ovarian cancer, Endometrioid endometrial cancer, CDK4/6, XPO1, SERD, Abemaciclib, Imlunestrant, Selinexor, Ovarian cancer, Endometrial cancer, LGSOC, EEC
Medical subject headings
Endometrial Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ImlunestrantDrug

    Oral study drug Taken once per day

  • AbemaciclibDrug

    Oral study drug Taken twice per day

  • SelinexorDrug

    Oral study drug Taken once per week

Study groups in NCT07832227
Study groupRoleWhat they receive
1A - Low grade serous ovarian cancer cohortExperimentalParticipants in Cohort 1A receive combination treatment with imlunestrant, abemaciclib, and selinexor. Treatment is outpatient, with a 14-day Cycle 0 followed by 28-day cycles.
Receives: Drug: Imlunestrant; Drug: Abemaciclib; Drug: Selinexor
1B - Endometrioid endometrial cancer cohortExperimentalParticipants in Cohort 1A receive combination treatment with imlunestrant, abemaciclib, and selinexor. Treatment is outpatient, with a 14-day Cycle 0 followed by 28-day cycles.
Receives: Drug: Imlunestrant; Drug: Abemaciclib; Drug: Selinexor

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)
  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

  5. Change in Ki67 Expression Rate from Cycle 0 to Cycle 2

    Ki67 expression rate is assessed by immunohistochemistry (IHC) and quantified as the proportion of positive tumor cells in paired on-treatment tumor biopsy samples collected before and after the addition of selinexor.

    Measured: The first biopsy is collected on Day 8 of Cycle 0, and the second biopsy is collected on Day 1 of Cycle 2. Cycle 0 is 14 days, and Cycles 1 and 2 are 28 days each.

  6. Change in pRB Expression Rate from Cycle 0 to Cycle 2

    pRB expression rate is assessed by IHC and quantified as the proportion of positive tumor cells in paired on-treatment tumor biopsy samples collected before and after the addition of selinexor.

    Measured: The first biopsy is collected on Day 8 of Cycle 0, and the second biopsy is collected on Day 1 of Cycle 2. Cycle 0 is 14 days, and Cycles 1 and 2 are 28 days each.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion1 Dec 2028 (estimated)
  4. Study completion1 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07832227
Sponsor's protocol ID
26-444
Acronym
SIERRA
Status last verified
Sep 2026
First submitted
14 Sep 2026
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imlunestrant, Abemaciclib and Selinexor in people with Low Grade Ovarian Serous Adenocarcinoma and Endometrial Cancer, run by Dana-Farber Cancer Institute.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Panagiotis Konstantinopoulos, MD, PhD (6176322334, Panagiotis_Konstantinopoulos@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Treatment duration depends on individual response, evidence of disease progression, and treatment tolerance. On average, up to 1 year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.

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