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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Urothelial Cancer; Poorly Differentiated Neuroendocrine Carcinomas; Homologous Recombination Deficient-Positive Malignancies Agnostic
• Intervention / Treatment: Drug: Lurbinectedin

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Sarah Cannon, Florida Cancer Specialist
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Kentucky
    • Pikeville, Kentucky, United States, 41501
      • Pikeville Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43219
      • Sarah Cannon, Zangmeister Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center Investigational Drug Service
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Bon Secours Hematology and Oncology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon, Tennesse Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. ≥ 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Adequate organ and bone marrow function
5. Has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

6. 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
7. Adequate contraceptive precautions

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Lurbinectedin; Monotherapy; Urothelial cancer; Poorly differentiated neuroendocrine carcinomas; Homologous recombination deficient-positive malignancies agnostic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Neoplasms; Carcinoma, Neuroendocrine
• Other Study ID Numbers: JZP712-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No