Endometrial CancerPhase 1/2LiDerNCT06385548
Efficacy and Safety Study of Lurbinectedin and Dostarlimab in Cancer Patients: Protocol VHIO21001 - LiDer
A Phase 1/2 study testing Lurbinectedin and Dostarlimab in people with Endometrial Cancer, run by Vall d'Hebron Institute of Oncology.
Trial summary
Background: Endometrial cancer is a prevalent gynecological malignancy, with a significant number of cases diagnosed at an advanced stage or recurring following initial treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- Lurbinectedin and Dostarlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2024to Apr 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged 18 years or older.
- Histologically confirmed advanced or recurrent endometrial cancer.
- Disease progression following prior platinum-based chemotherapy.
- Adequate organ function, including bone marrow, renal, and hepatic function.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Measurable disease per RECIST v.1.1 criteria.
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- Availability of archival tumor tissue sample or willingness to undergo a tumor biopsy.
- Signed informed consent form.
- Life expectancy of at least 3 months.
- Willingness and ability to comply with study procedures and follow-up visits.
- Agreement to use effective contraception during the study period and for a specified duration thereafter if applicable.
Who cannot join
- Prior treatment with lurbinectedin or dostarlimab.
- Active autoimmune disease requiring systemic treatment.
- Symptomatic or untreated central nervous system metastases.
- History of interstitial lung disease or pneumonitis requiring steroids.
- Uncontrolled concurrent illness or medical condition.
- History of Grade ≥3 immune-related adverse events with prior immunotherapy.
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- Pregnancy or breastfeeding.
- Concurrent treatment with other anticancer therapy.
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- Concurrent treatment with corticosteroids exceeding a specified dose or duration.
- Participation in another clinical trial involving investigational therapy within a specified timeframe.
- Any other condition that, in the investigator's opinion, would compromise the patient's safety or interfere with the study conduct.
About this study
Official title: Phase I-II Study to Evaluate the Safety, Tolerability, and Efficacy of Lurbinectedin and Dostarlimab in Patients with Advanced/Recurrent Endometrial Cancer with Disease Progression Following Previous Platinum Chemotherapy Therapy
Background:
Endometrial cancer is a prevalent gynecological malignancy, with a significant number of cases diagnosed at an advanced stage or recurring following initial treatment. Platinum-based chemotherapy represents a standard treatment option for these patients; however, disease progression often occurs, highlighting the need for novel therapeutic approaches. Lurbinectedin, a synthetic analog of marine alkaloid-derived compounds, and dostarlimab, a monoclonal antibody targeting PD-1, have demonstrated promising antitumor activity in various malignancies. This phase I-II clinical trial seeks to evaluate the safety, tolerability, and efficacy of combining lurbinectedin and dostarlimab in patients with advanced or recurrent endometrial cancer who have experienced disease progression following platinum-based chemotherapy.
Read more
Primary Objectives:
To determine the maximum tolerated dose (MTD) and recommended dose for further investigation of lurbinectedin and dostarlimab in combination therapy for advanced or recurrent endometrial cancer.
To assess the antitumor activity of lurbinectedin and dostarlimab combination therapy, measured by objective response rate (ORR), in patients with advanced or recurrent endometrial cancer.
Secondary Objectives:
To evaluate the safety and tolerability of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer.
To characterize the pharmacokinetic profile of lurbinectedin and dostarlimab when administered in combination therapy.
To explore pharmacogenomic biomarkers predictive of response and/or resistance to lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer.
To assess progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS) in patients receiving lurbinectedin and dostarlimab combination therapy for advanced or recurrent endometrial cancer.
To investigate the impact of lurbinectedin and dostarlimab combination therapy on quality of life and symptom control in patients with advanced or recurrent endometrial cancer.
Read the detailed description
This study is a phase I-II clinical trial conducted to evaluate the safety, tolerability, and efficacy of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer. The trial follows a multicenter, open-label design and comprises two phases: a dose escalation phase (Phase I) and an expansion phase (Phase II). The primary endpoints include determining the maximum tolerated dose (MTD), recommended dose for further investigation, and objective response rate (ORR). Secondary endpoints encompass safety, pharmacokinetics, pharmacogenomics, progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), overall survival (OS), and quality of life assessments.
Study Treatments:
Lurbinectedin: Lurbinectedin is administered as a lyophilized powder for concentrate for infusion, reconstituted with sterile water for injection to achieve a concentration of 0.5 mg/mL. The initial dose for infusion is 2.6 mg/m^2, diluted in either 5% glucose solution or 0.9% sodium chloride solution. During Phase I, dose adjustments are based on body surface area calculated using the DuBois formula.
Dostarlimab: Dostarlimab is supplied in vials containing 500 mg at a concentration of 50 mg/mL. The recommended dose is a fixed dose of 500 mg administered intravenously over 30 minutes. Treatment cycles consist of administration on Day 1 of a 21-day cycle, with dostarlimab followed by lurbinectedin in combination therapy.
During the dose escalation phase (Phase I), a predefined dose escalation scheme is employed, starting with dose level (DL) -1 and progressing to DL1, DL2, and subsequent levels as per the protocol. Dose escalation is guided by the occurrence of dose-limiting toxicities (DLTs) and the determination of the MTD. Once the MTD is established, the expansion phase (Phase II) begins, wherein additional patients receive treatment at the recommended dose to further evaluate safety and efficacy outcomes.
- Conditions
- Endometrial Cancer
- Being tested
- Lurbinectedin, Dostarlimab
- Keywords
- endometrial cancer, lurbinectedin, dostarlimab
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LurbinectedinDrug
participants will receive intravenous infusions of lurbinectedin at a dose of 2.6 mg/m², diluted in a minimum of 100 mL of either 5% glucose solution or 0.9% sodium chloride solution. The infusion will last for one hour and will be administered every three weeks.
DostarlimabDrug
participants will receive intravenous infusions of dostarlimab at a fixed dose of 500 mg, administered over 30 minutes on Day 1 of each three-week cycle.
| Study group | Role | What they receive |
|---|---|---|
| Lurbinectedin and Dostarlimab Combination Therapy | Experimental | Not described Receives: Drug: Lurbinectedin; Drug: Dostarlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) Determination
This measure involves identifying the highest dose of lurbinectedin in combination with dostarlimab that can be administered without causing unacceptable toxicity. The recommended dose for further evaluation in Phase II will also be determined.
Measured: MTD and RD will be assessed during the Phase I portion of the study, the time frame will be arround 6 months.
Evaluation of Lurbinectedin and Dostarlimab Combination Therapy in Advanced/Recurrent Cervical Cancer Patients
This objective aims to assess the efficacy of lurbinectedin in combination with dostarlimab in advanced or recurrent cervical cancer patients who have experienced disease progression after platinum-based chemotherapy. The primary objective is to evaluate the confirmed tumor response rate, as defined by RECIST v1.1 criteria, in patients without alterations in the MMR system.
Measured: This objective will be assessed during the Phase II portion of the study, the time frame will be arround 6 months.
Secondary outcomes (6)
Safety Evaluation of Lurbinectedin in combination with Dostarlimab
Safety will be assessed by monitoring adverse events (AEs) using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Measured: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 1 year
Evaluate the progression-free survival (PFS)
Evaluate the time from study entry until disease progression or death from any cause.
Measured: These efficacy endpoints will be evaluated throughout the study, with regular assessments during follow-up visits, up to 1 year
Pharmacokinetic (PK) and Pharmacogenomic Evaluation
PK parameters will be assessed to determine the drug's concentration in plasma over time.
Measured: PK and pharmacogenomic evaluations will occur at specified time points during the study (12 months).
Overall Response Rate (ORR)
The proportion of patients with a complete or partial response to treatment, assessed by RECIST v.1.1 criteria, specifically in the Phase II portion of the study.
Measured: ORR will be assessed after completion of treatment cycles and response evaluations according to RECIST v.1.1 criteria(1 year).
Evaluate the Duration of Response (DOR)
The objective is to analyse the time from the first documented response until disease progression or death.
Measured: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 1 year
Evaluate the Clinical Benefit Rate (CBR)
The objective is to examinate the time from study entry until death from any cause. Survival Rates: The percentage of patients who survive at specified time points (6, 12, 18, and 24 months)
Measured: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2024
- Study startMay 2024 (estimated)
- Primary completion1 May 2024
- Study completionApr 2026 (estimated)
Why it stopped: IMP owner decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vall d'Hebron Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06385548
- Sponsor's protocol ID
- VHIO21001
- Acronym
- LiDer
- Status last verified
- Apr 2024
- First submitted
- 11 Apr 2024
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study to Evaluate the Safety, Tolerability, and Efficacy of Lurbinectedin and Dostarlimab in Patients with Advanced/Recurrent Endometrial Cancer with Disease Progression Following Previous Platinum Chemotherapy Therapy
- ClinicalTrials.gov ID
- NCT06385548
- Acronym / sponsor ID
- LiDer / VHIO21001
- Conditions
- Endometrial Cancer
- Keywords
- endometrial cancer, lurbinectedin, dostarlimab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: IMP owner decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vall d'Hebron Institute of OncologyUniversity, hospital or other
- Study start
- May 2024 (estimated)
- Primary completion
- 1 May 2024 (actual)
- Study completion
- Apr 2026 (estimated)
- First posted
- 26 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Endometrial cancer is a prevalent gynecological malignancy, with a significant number of cases diagnosed at an advanced stage or recurring following initial treatment. Platinum-based chemotherapy represents a standard treatment option for these patients; however, disease progression often occurs, highlighting the need for novel therapeutic approaches. Lurbinectedin, a synthetic analog of marine alkaloid-derived compounds, and dostarlimab, a monoclonal antibody targeting PD-1, have demonstrated promising antitumor activity in various malignancies. This phase I-II clinical trial seeks to evaluate the safety, tolerability, and efficacy of combining lurbinectedin and dostarlimab in patients with advanced or recurrent endometrial cancer who have experienced disease progression following platinum-based chemotherapy.
Primary Objectives:
To determine the maximum tolerated dose (MTD) and recommended dose for further investigation of lurbinectedin and dostarlimab in combination therapy for advanced or recurrent endometrial cancer.
To assess the antitumor activity of lurbinectedin and dostarlimab combination therapy, measured by objective response rate (ORR), in patients with advanced or recurrent endometrial cancer.
Secondary Objectives:
To evaluate the safety and tolerability of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer.
To characterize the pharmacokinetic profile of lurbinectedin and dostarlimab when administered in combination therapy.
To explore pharmacogenomic biomarkers predictive of response and/or resistance to lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer.
To assess progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS) in patients receiving lurbinectedin and dostarlimab combination therapy for advanced or recurrent endometrial cancer.
To investigate the impact of lurbinectedin and dostarlimab combination therapy on quality of life and symptom control in patients with advanced or recurrent endometrial cancer.
Detailed description
This study is a phase I-II clinical trial conducted to evaluate the safety, tolerability, and efficacy of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer. The trial follows a multicenter, open-label design and comprises two phases: a dose escalation phase (Phase I) and an expansion phase (Phase II). The primary endpoints include determining the maximum tolerated dose (MTD), recommended dose for further investigation, and objective response rate (ORR). Secondary endpoints encompass safety, pharmacokinetics, pharmacogenomics, progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), overall survival (OS), and quality of life assessments.
Study Treatments:
Lurbinectedin: Lurbinectedin is administered as a lyophilized powder for concentrate for infusion, reconstituted with sterile water for injection to achieve a concentration of 0.5 mg/mL. The initial dose for infusion is 2.6 mg/m^2, diluted in either 5% glucose solution or 0.9% sodium chloride solution. During Phase I, dose adjustments are based on body surface area calculated using the DuBois formula.
Dostarlimab: Dostarlimab is supplied in vials containing 500 mg at a concentration of 50 mg/mL. The recommended dose is a fixed dose of 500 mg administered intravenously over 30 minutes. Treatment cycles consist of administration on Day 1 of a 21-day cycle, with dostarlimab followed by lurbinectedin in combination therapy.
During the dose escalation phase (Phase I), a predefined dose escalation scheme is employed, starting with dose level (DL) -1 and progressing to DL1, DL2, and subsequent levels as per the protocol. Dose escalation is guided by the occurrence of dose-limiting toxicities (DLTs) and the determination of the MTD. Once the MTD is established, the expansion phase (Phase II) begins, wherein additional patients receive treatment at the recommended dose to further evaluate safety and efficacy outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lurbinectedin and Dostarlimab Combination Therapy | Experimental | Drug: Lurbinectedin, Drug: Dostarlimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adult patients aged 18 years or older.
- Histologically confirmed advanced or recurrent endometrial cancer.
- Disease progression following prior platinum-based chemotherapy.
- Adequate organ function, including bone marrow, renal, and hepatic function.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (12 listed)
- Prior treatment with lurbinectedin or dostarlimab.
- Active autoimmune disease requiring systemic treatment.
- Symptomatic or untreated central nervous system metastases.
- History of interstitial lung disease or pneumonitis requiring steroids.
- Uncontrolled concurrent illness or medical condition.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lurbinectedinparticipants will receive intravenous infusions of lurbinectedin at a dose of 2.6 mg/m², diluted in a minimum of 100 mL of either 5% glucose solution or 0.9% sodium chloride solution. The infusion will last for one hour and will be administered every three weeks. | Drug | Lurbinectedin and Dostarlimab Combination Therapy |
| Dostarlimabparticipants will receive intravenous infusions of dostarlimab at a fixed dose of 500 mg, administered over 30 minutes on Day 1 of each three-week cycle. | Drug | Lurbinectedin and Dostarlimab Combination Therapy |
Primary outcome
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) Determination
Time frame: MTD and RD will be assessed during the Phase I portion of the study, the time frame will be arround 6 months.
This measure involves identifying the highest dose of lurbinectedin in combination with dostarlimab that can be administered without causing unacceptable toxicity. The recommended dose for further evaluation in Phase II will also be determined.
Evaluation of Lurbinectedin and Dostarlimab Combination Therapy in Advanced/Recurrent Cervical Cancer Patients
Time frame: This objective will be assessed during the Phase II portion of the study, the time frame will be arround 6 months.
This objective aims to assess the efficacy of lurbinectedin in combination with dostarlimab in advanced or recurrent cervical cancer patients who have experienced disease progression after platinum-based chemotherapy. The primary objective is to evaluate the confirmed tumor response rate, as defined by RECIST v1.1 criteria, in patients without alterations in the MMR system.
6 secondary outcomes
Safety Evaluation of Lurbinectedin in combination with Dostarlimab
Time frame: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 1 year
Evaluate the progression-free survival (PFS)
Time frame: These efficacy endpoints will be evaluated throughout the study, with regular assessments during follow-up visits, up to 1 year
Pharmacokinetic (PK) and Pharmacogenomic Evaluation
Time frame: PK and pharmacogenomic evaluations will occur at specified time points during the study (12 months).
Overall Response Rate (ORR)
Time frame: ORR will be assessed after completion of treatment cycles and response evaluations according to RECIST v.1.1 criteria(1 year).
Evaluate the Duration of Response (DOR)
Time frame: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 1 year
Evaluate the Clinical Benefit Rate (CBR)
Time frame: Safety evaluations will occur throughout the study, starting from the first dose administration and continuing until the end of the study, an average of 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lurbinectedin and Dostarlimab in people with Endometrial Cancer, run by Vall d'Hebron Institute of Oncology.
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 11 inclusion and 12 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: withdrawn, as of the sponsor's last update on 1 Apr 2025. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) and Recommended Dose (RD) Determination (time frame: MTD and RD will be assessed during the Phase I portion of the study, the time frame will be arround 6 months.). The study lists 2 primary outcomes in all. 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 1 Apr 2025.