Lurbinectedin Monotherapy in Participants With Advanced or Metastatic Solid Tumors (EMERGE-201)

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

Detailed Description
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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.

Official Title
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EMERGE-201: A Phase 2, Multicenter, Open-label Study of Lurbinectedin Efficacy and Safety in Participants With Advanced or Metastatic Solid Tumors

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

Intervention / Treatment
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* Drug: Lurbinectedin


Participation Criteria
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Eligibility Criteria
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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: Histologically or cytologically confirmed urothelial cancer Histologically or cytologically confirmed poorly differentiated neuroendocrine carcinoma 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urothelial Cancer Cohort<br>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. | Drug: Lurbinectedin<br>* Lurbinectedin 3.2 mg/m^2 intravenous (IV) every 3 weeks (Q3W)<br>|
| Experimental: Poorly Differentiated Neuroendocrine Carcinomas Cohort<br>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. | Drug: Lurbinectedin<br>* Lurbinectedin 3.2 mg/m^2 intravenous (IV) every 3 weeks (Q3W)<br>|
| Experimental: Homologous Recombination Deficient-Positive Malignancies Agnostic Cohort<br>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. | Drug: Lurbinectedin<br>* Lurbinectedin 3.2 mg/m^2 intravenous (IV) every 3 weeks (Q3W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-Assessed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 | 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. | Baseline to disease progression or death, up to 36 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-Assessed Progression Free Survival (PFS) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 | 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. | Baseline to disease progression or death, up to 36 weeks. | 
| Investigator-Assessed Time-To-Response (TTR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 | 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. | Baseline to disease progression or death, up to 36 weeks. | 
| Investigator-Assessed Duration of response (DOR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 | 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. | Baseline to disease progression or death, up to 36 weeks. | 
| Investigator-assessed Disease Control Rate (DCR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 | 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. | Baseline to disease progression or death, up to 36 weeks. | 
| Overall Survival (OS) in Participants Treated with Lurbinectedin | 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. | Baseline and every 3 months, up to 16 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lurbinectedin, Monotherapy, Urothelial cancer, Poorly differentiated neuroendocrine carcinomas, Homologous recombination deficient-positive malignancies agnostic