Lurbinectedin Monotherapy in Participants With Advanced or Metastatic Solid Tumors

Phase 2

Terminated

Conditions: Advanced Solid Tumor
Poorly Differentiated Neuroendocrine Carcinomas
Urothelial Cancer
Metastatic Solid Tumor
Homologous Recombination Deficient-Positive Malignancies Agnostic

Interventions: Drug: Lurbinectedin

Registration Number: NCT05126433

Lead Sponsor: Jazz Pharmaceuticals

Brief Summary: This is an open-label, multicenter, phase 2 study of lurbinectedin monotherapy in participants with advanced (metastatic and/or unresectable) solid tumors.

Detailed Description: This phase 2, multicenter, open-label study is designed to assess the safety and efficacy of lurbinectedin monotherapy in 3 cohorts of participants with high-unmet medical need: advanced (metastatic and/or unresectable) urothelial cancer (UC), poorly differentiated neuroendocrine carcinomas (PD-NEC), and a homologous recombination deficient-positive malignancies agnostic cohort.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 47

Inclusion Criteria

Signed informed consent
≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ and bone marrow function
Has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Have advanced (metastatic/unresectable) cancers in one of the following:
1. Histologically or cytologically confirmed urothelial cancer
2. Histologically or cytologically confirmed poorly differentiated neuroendocrine carcinoma
3. Histologically or cytologically confirmed homologous recombination deficient-positive malignancies agnostic, which may include endometrial, biliary tract, urothelial, breast (TNBC or HR+HER2- breast cancer), pancreas, gastric, or esophageal solid tumors with preidentified germline and/or somatic pathogenic mutation
Adequate contraceptive precautions

Exclusion Criteria

Known symptomatic central nervous system (CNS) metastasis requiring steroids
History of prior malignancy within 2 years of enrollment
Clinically significant cardiovascular disease
Active infection requiring systemic therapy
Significant non-neoplastic liver disease
Prior treatment with trabectedin or lurbinectedin
Treatment with an investigational agent within 4 weeks of enrollment
Received live vaccine with 4 weeks of first dose
Prior allogeneic bone marrow or solid organ transplant
Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
Positive human immunodeficiency virus (HIV) infection at screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Urothelial Cancer Cohort	Lurbinectedin	Participants with advanced (metastatic and/or unresectable) urothelial carcinoma who have progressed on platinum-containing regimen (prior therapies may include but are not limited to immune checkpoint inhibitor, enformumab vendotin, or sacituzumab govitecan) will receive Lurbinectedin 3.2 mg/m\^2 intravenous (IV) on Day 1 of every 3 weeks (Q3W) cycle until confirmed disease progression, withdrawal of participant consent, participant lost to follow-up, unacceptable toxicity, or the study or individual cohort may be terminated by the sponsor for lack of efficacy signal or any other reason.
Poorly Differentiated Neuroendocrine Carcinomas Cohort	Lurbinectedin	Participants with advanced (metastatic and/or unresectable) poorly differentiated neuroendocrine carcinomas who received at least 1 prior line of therapy will receive Lurbinectedin 3.2 mg/m\^2 intravenous (IV) on Day 1 of every 3 weeks (Q3W) cycle until confirmed disease progression, withdrawal of participant consent, participant lost to follow-up, unacceptable toxicity, or the study or individual cohort may be terminated by the sponsor for lack of efficacy signal or any other reason.
Homologous Recombination Deficient-Positive Malignancies Agnostic Cohort	Lurbinectedin	Participants with advanced (metastatic and/or unresectable) endometrial, biliary tract, urothelial, breast (TNBC or HR+HER2- breast cancer), pancreas, gastric, or esophageal solid tumors with preidentified germline and/or somatic pathogenic mutation and received at least 1 prior line of therapy will receive Lurbinectedin 3.2 mg/m\^2 intravenous (IV) on Day 1 of every 3 weeks (Q3W) cycle until confirmed disease progression, withdrawal of participant consent, participant lost to follow-up, unacceptable toxicity, or the study or individual cohort may be terminated by the sponsor for lack of efficacy signal or any other reason.

Primary Outcome Measures

Name	Time	Method
Investigator-Assessed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Baseline to disease progression or death, up to 36 weeks.	The ORR is defined as the proportion of participants whose best overall response (BOR) is investigator-assessed confirmed complete response (CR) or partial response (PR) using the RECIST v1.1 criteria. BOR is defined as the best response recorded between the date of first dose and the date of objectively documented progression per RECIST v1.1, or the date of subsequent anticancer therapy, death due to any cause, loss to follow-up, or study discontinuation, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Investigator-Assessed Progression Free Survival (PFS) as Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Baseline to disease progression or death, up to 36 weeks	PFS is defined as the time from the first dosing date to the date of first documented disease progression or death due to any cause, whichever occurs first.
Investigator-Assessed Time-To-Response (TTR) as Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Baseline to disease progression or death, up to 36 weeks	TTR is defined as the time from the first dosing date to the date of the first confirmed response (complete response \[CR\] or partial response \[PR\]), as assessed by the investigators.
Investigator-Assessed Duration of Response (DOR) as Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Baseline to disease progression or death, up to 36 weeks	DOR is defined as the time from the first confirmed response (complete response \[CR\] or partial response \[PR\]) to the date of the first documented tumor progression as determined using RECIST v1.1 criteria or death due to any cause, whichever occurs first
Investigator-assessed Disease Control Rate (DCR) as Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Baseline to disease progression or death, up to 36 weeks.	DCR is defined as the proportion of participants whose best overall response (BOR) is confirmed complete response (CR), or partial response (PR), or stable disease (SD) using the RECIST v1.1 criteria.
Overall Survival (OS) in Participants Treated With Lurbinectedin	Baseline and every 3 months, up to 16 months	OS is defined as the time from the first dosing date to the date of death from any cause. A participant who has not died will be censored at the last known alive date

Trial Locations

Locations (17): Stanford Cancer Center
🇺🇸
Stanford, California, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Bon Secours Hematology and Oncology
🇺🇸
Greenville, South Carolina, United States
Florida Cancer Specialists
🇺🇸
Fort Myers, Florida, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
🇺🇸
Omaha, Nebraska, United States
Sarah Cannon, Zangmeister Cancer Center
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center Investigational Drug Service
🇺🇸
Pittsburgh, Pennsylvania, United States
Sarah Cannon, Tennesse Oncology
🇺🇸
Nashville, Tennessee, United States
MD Anderson
🇺🇸
Houston, Texas, United States
Inova Schar Cancer Institute
🇺🇸
Fairfax, Virginia, United States
Pikeville Medical Center
🇺🇸
Pikeville, Kentucky, United States
Sarah Cannon, Florida Cancer Specialist
🇺🇸
Saint Petersburg, Florida, United States
Eastern Connecticut Hematology and Oncology
🇺🇸
Norwich, Connecticut, United States
Dana Farber
🇺🇸
Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States