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

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.

Sex

All

Minimum age

18 Years

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.