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

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05126433

Collaborator

(none)

Enrollment

Locations

Arms

27.7

Anticipated Duration (Months)

5.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Metastatic Solid Tumor Urothelial Carcinoma Large Cell Neuroendocrine Carcinoma of the Lung Homologous Recombination Deficiency	Drug: Lurbinectedin	Phase 2

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), large cell neuroendocrine tumor (LCNET) of lung, and a tumor agnostic cohort of participants with homologous recombination deficient (HRD) positive malignancies.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 3, 2022

Anticipated Primary Completion Date :

Nov 23, 2023

Anticipated Study Completion Date :

Jun 23, 2024

Arms and Interventions

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: Large Neuroendocrine Tumor of the Lung Cohort Participants with advanced (metastatic and/or unresectable) large neuroendocrine tumor of the lung who have progressed on platinum-containing regimen (prior treatment with immune checkpoint is allowed) 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 Solid Tumor Malignancy 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 no more than 3 prior lines of chemotherapies for advanced/metastatic disease 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)

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: Large Neuroendocrine Tumor of the Lung Cohort

Participants with advanced (metastatic and/or unresectable) large neuroendocrine tumor of the lung who have progressed on platinum-containing regimen (prior treatment with immune checkpoint is allowed) 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 Solid Tumor Malignancy 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 no more than 3 prior lines of chemotherapies for advanced/metastatic disease 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)

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 large cell neuroendocrine tumor of lung
Histologically or cytologically confirmed homologous recombination deficient (HRD) positive 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eastern Connecticut Hematology and Oncology	Norwich	Connecticut	United States	06360
2	Sarah Cannon, Florida Cancer Specialist	Saint Petersburg	Florida	United States	33705
3	Dana Farber	Boston	Massachusetts	United States	02215
4	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68124
5	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
6	Sarah Cannon, Zangmeister Cancer Center	Columbus	Ohio	United States	43219
7	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
8	UPMC Hillman Cancer Center Investigational Drug Service	Pittsburgh	Pennsylvania	United States	15232
9	Bon Secours Hematology and Oncology	Greenville	South Carolina	United States	29607
10	Sarah Cannon, Tennesse Oncology	Nashville	Tennessee	United States	37203
11	MD Anderson	Houston	Texas	United States	77030