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

NCT06385548 | Withdrawn Phase 1

• 1 other identifier: VHIO21001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Endometrial Cancer

Keywords

endometrial cancer; lurbinectedin; dostarlimab

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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 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)

  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 and pharmacogenomic evaluations will occur at specified time points during the study (12 months).

• Overall Response Rate (ORR)

  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)

  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

Study Arms (1)

Lurbinectedin and Dostarlimab Combination Therapy

EXPERIMENTAL

Drug: Lurbinectedin; Drug: Dostarlimab

Interventions

Lurbinectedin DRUG

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.

Lurbinectedin and Dostarlimab Combination Therapy

Dostarlimab DRUG

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.

Lurbinectedin and Dostarlimab Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

PM 01183; dostarlimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2024
• First Posted: April 26, 2024
• Study Start: May 1, 2024
• Primary Completion: May 1, 2024
• Study Completion: April 1, 2026
• Last Updated: April 1, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share