Efficacy and Safety Study of Lurbinectedin and Dostarlimab in Cancer Patients: Protocol VHIO21001 - LiDer (LiDer)

March 26, 2025 updated by: Vall d'Hebron Institute of Oncology

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.

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lurbinectedin and Dostarlimab Combination Therapy
Drug: Lurbinectedin
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.
Drug: Dostarlimab
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
This objective will be assessed during the Phase II portion of the study, the time frame will be arround 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
Evaluate the time from study entry until disease progression or death from any cause.
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).
PK parameters will be assessed to determine the drug's concentration in plasma over time.
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).
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.
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
The objective is to analyse the time from the first documented response until disease progression or death.
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
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)
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vall d'Hebron Institute of Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Actual)

May 1, 2024

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

April 11, 2024

First Submitted That Met QC Criteria

April 23, 2024

First Posted (Actual)

April 26, 2024

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 26, 2025

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VHIO21001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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