Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)

NCT06228066 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001523001523-C
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin and avelumab are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET. Objective: To test lurbinectedin with or without avelumab in people with SCCB or HGNET. Eligibility: Adults aged 18 years and older with SCBB or HGNET that returned and spread after treatment. Design: Participants will be screened. They will have a physical exam. They will have blood tests and imaging scans. They may need to have a new biopsy: A small needle will be used to collect a tissue sample from the tumor. Both study drugs are given through a tube attached to a needle inserted into a vein. If participants have already received a drug like avelumab they will receive only lurbinectedin. If patients have not been previously treated with a drug like avelumab they will receive both lurbinectedin and avelumab. All participants will receive their treatment once every 3 weeks for up to 10 years. They will also receive other drugs to relieve adverse effects. Biopsies, blood tests, and imaging scans will be repeated during some study visits. Participants may also have urine tests and tests of their heart function. Participants may remain in the study as long as the treatment is helping them. If they stop treatment, they will have safety visits 14, 30, and 90 days after their last dose. Additional follow-up visits will continue 5 to 10 years.

Conditions

Small Cell Carcinoma of the Bladder; High Grade Neuroendocrine Tumors of the Urinary Tract

Keywords

High grade neuroendocrine tumors; small cell neuroendocrine carcinoma; large cell neuroendocrine carcinoma; transcription factor inhibitor; Immunotherapy; programmed cell death 1 ligand 1

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy

  At every restaging (prior to every 3rd cycle) until the end of the treatment

Secondary Outcomes (5)

• Safety of lurbinectedin with or without avelumab

  From first dose through 90 days after last treatment with the study drug(s)

• Clinical benefit rate (CBR)

  At every restaging (every 9 weeks) until the end of the study therapy

• Progression-free survival (PFS)

  At every restaging (every 9 weeks) until PD

• Overall survival (OS)

  Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 10 years after the end of therapy.

• Duration of response (DoR)

  At each study visit and at every restaging (every 9 weeks) starting at cycle 3 until PD

Study Arms (2)

Arm 1

EXPERIMENTAL

Treatment with lurbinectedin

Drug: Lurbinectedin

Arm 2

EXPERIMENTAL

Treatment with lurbinectedin and avelumab

Drug: Lurbinectedin; Drug: Avelumab

Interventions

Lurbinectedin DRUG

Lurbinectedin is administered IV over 1 hour at 3.2 mg/m\^2 on day 1 of each 21-day cycle

Arm 1; Arm 2

Avelumab DRUG

Avelumab is administered IV at 800 mg over 1 hour on day 1 of each 21-day cycle

Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior treatment as follows:
• For Cohort 1: Participants must have received prior ICIs (PD-1 or PD-L1) or be ineligible for treatment with ICIs.
• For Cohort 2: Participants must be ICI naive but eligible to receive them.
• Participants must have metastatic disease defined as new or progressive lesions.
• Participants must have at least one measurable site of disease, per RECIST 1.1.
• Participants must have received, be ineligible, or refused prior platinum/etoposide chemotherapy for SCCB or other HGNET of the urinary tract. Platinum ineligibility is defined as a CrCl \<30, or two or more of the following: CrCl \<50-60, ECOG \>=2, hearing loss \>= grade 2, peripheral neuropathy \>= grade 2, New York Heart Association (NYHA) heart failure class \>= class III.
• Age \>=18 years.
• Eastern Cooperative Oncology Group \[ECOG\] performance status (PS) \<=2 (Karnofsky \>=60%).
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>=1,500/microliter
• Platelets \>=100,000/ microliter
• Hemoglobin (Hgb) \> 9g/dL (erythrocyte transfusions are allowed to achieve acceptable Hgb)
• Total bilirubin within normal limits with the following exceptions:
• Participants with tumor involving the liver may have mild to moderate hepatic impairment with total bilirubin \<= 1.5 x upper limit of normal (ULN)
• Participants with known Gilbert disease who have serum bilirubin level \<= 1.5 x ULN

You may not qualify if:

• Prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 14 days prior to the first drug administration. Additionally, FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) may be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the enrolling investigator prior to enrollment.
• Participants previously treated with lurbinectedin.
• History of anaphylactic allergic reactions attributed to compounds of similar chemical or biologic composition to lurbinectedin or avelumab
• Symptomatic or untreated CNS metastases
• For Cohort 2: Active autoimmune disease that might deteriorate when receiving avelumab with the exception of:
• Diabetes type I, eczema, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment
• Requirement of hormone replacement with corticosteroids if the steroids are administered only for the purpose of hormonal replacement and at doses \<= 10mg of prednisone or equivalent per day
• Requirement of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation)
• Physiologic doses of corticosteroids (\<= the equivalent of prednisone 10 mg/day). The use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to treatment initiation and on study.
• Prior organ transplantation including allogenic stem cell transplantation.
• Participants who have received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus and locally authorized/approved COVID-19 vaccines are permitted.
• Pregnant people as evaluated by a positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test
• Severe uncontrolled intercurrent illness that would limit compliance with study requirements, evaluated by history, physical exam, and chemistry panel.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Simon N, Chandran E, Atiq S, Kydd AR, Girardi D, Ley L, Cordes L, Wang TF, Boudjadi S, Stukes I, Smith E, Akbulut D, Niglio S, Patel R, Banday R, Redd B, Gurram S, Steinberg S, Apolo AB. A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (laser)-design and rationale. Future Oncol. 2025 Apr;21(10):1171-1177. doi: 10.1080/14796694.2025.2480534. Epub 2025 Mar 21.

  PMID: 40116623 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

PM 01183; avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCIMO Referral Office

CONTACT

(888) 624-1937; ncimo_referrals@mail.nih.gov

Andrea B Apolo, M.D.

CONTACT

(301) 480-0536; apoloab@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: January 29, 2024
• Study Start: June 13, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)