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Trial Title:
Efficacy and Safety Study of Lurbinectedin and Dostarlimab in Cancer Patients: Protocol VHIO21001 - LiDer
NCT ID:
NCT06385548
Condition:
Endometrial Cancer
Conditions: Official terms:
Endometrial Neoplasms
Dostarlimab
Conditions: Keywords:
endometrial cancer
lurbinectedin
dostarlimab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lurbinectedin
Description:
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.
Arm group label:
Lurbinectedin and Dostarlimab Combination Therapy
Intervention type:
Drug
Intervention name:
Dostarlimab
Description:
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.
Arm group label:
Lurbinectedin and Dostarlimab Combination Therapy
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.
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
May 2024
Completion date:
April 2026
Lead sponsor:
Agency:
Vall d'Hebron Institute of Oncology
Agency class:
Other
Source:
Vall d'Hebron Institute of Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06385548
