Selinexor and Pembrolizumab for the Treatment of Cisplatin-Ineligible or Cisplatin-Refractory Locally Advanced or Metastatic Urothelial Carcinoma

NCT04856189 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: UCDCC#289NCI-2021-02845P30CA093373
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial finds the best dose of selinexor and its effect with pembrolizumab in treating patients with urothelial carcinoma that are not eligible to receive the chemotherapy drug cisplatin, or have been given cisplatin and the cancer has gotten worse. Patients must also have urothelial carcinoma that has spread locally, near where it started (locally advanced), or has spread to other parts of the body (metastatic). Selinexor may stop the growth of tumor cells by blocking a protein, called XPO1, that is needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving selinexor and pembrolizumab may kill more tumor cells.

Conditions

Advanced Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Refractory Urothelial Carcinoma; Locally Advanced Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) (Phase Ib)

  Defined by dose-limiting toxicity (DLTs). Dose limiting toxicities will be listed according to dose level. Separately by dose level and the expansion cohort (as well as for the total RP2D cohort), adverse events (AEs) will be summarized as number of patients according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 term and grade, where grade is the maximum across a patient's treatment period.

  Up to 2 cycles (each cycle is 21 days); up to about 6 weeks

• Objective Response Rate (ORR) (Phase II)

  ORR, calculated as the total number of patients with a confirmed complete response or partial response, will be reported as a percentage of total evaluable patients. Response will be reported using Response Evaluation Criteria in Solid Tumor 1.1 definitions. ORR will be summarized by exact binomial 95% confidence intervals (CI).

  Up to approximately 2 years 4 months

Secondary Outcomes (2)

• Number of Patients Who Experience a Grade 3 or Higher Adverse Event (AE).

  Up to approximately 1 year 7 months.

• Progression-free Survival (PFS)

  From enrollment to trial to time of disease progression or death from any cause, assessed up to 2 year 4 months.

Study Arms (1)

Treatment (selinexor, pembrolizumab)

EXPERIMENTAL

Patients receive selinexor PO on days 1, 8 and 15, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Selinexor

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (selinexor, pembrolizumab)

Selinexor DRUG

Given PO

Also known as: ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio

Treatment (selinexor, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed locally advanced or metastatic urothelial carcinoma by histology
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Not eligible to receive cisplatin-based chemotherapy due to renal dysfunction (defined as creatinine clearance \[CrCl\] =\< 60 mL/min), \> grade 2 peripheral neuropathy, or ototoxicity (defined as \>= grade 2 hearing loss); OR unwillingness of patient to receive cisplatin; OR progressed on one platinum-based chemotherapy regimen for advanced disease
• May have had neoadjuvant or adjuvant platinum-based chemotherapy or intravesical therapy in the past
• \>= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
• Life expectancy \>= 3 months
• Absolute neutrophil count (ANC) \>= 1 × 10\^9/L
• Platelet count \>= 75 × 10\^9/L (patients for whom \<50% of bone marrow nucleated cells are plasma cells) or \>= 50,000/mm3 (patients for whom \>= 50% of bone marrow nucleated cells are plasma cells)
• Hemoglobin \>= 9 g/dL (may have been transfused)
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 x ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 2.5 x ULN, or AST and ALT levels =\< 5 x ULN (for subjects with documented metastatic disease to the liver)
• Creatinine clearance \>= 30 mL/min by Cockcroft-Gault formula
• Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for \> 8 weeks and viral load is \< 100 IU/mL prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed. Subjects with human immunodeficiency virus (HIV) who have CD4+ T-cell counts \>= 350 cells/uL and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed
• Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate archival tumor specimen available for PD-L1 IHC evaluation)

You may not qualify if:

• Receiving radiation =\< 14 days prior to enrollment to the site of selected target lesions
• Systemic therapy for cancer =\< 21 days prior to enrollment
• Autoimmune disorder requiring active therapy as defined by corticosteroids at a dose \>= 10 mg oral prednisone or the equivalent or requiring chronic immunosuppressive therapy
• Use of corticosteroids =\< 14 days prior to enrollment at a dose of \>= 10 mg oral prednisone or the equivalent per day
• Received immune checkpoint inhibitor therapy (anti-PD-1, anti-PD-L1, or anti-CTLA4 directed therapy) on a prior clinical trial
• Has received selinexor or another XPO1 inhibitor previously
• Any active gastrointestinal dysfunction that could interfere with absorption of study treatment in the opinion of the investigator
• Pregnant or lactating women
• Any condition that would prohibit the understanding or rendering of informed consent
• Any condition including additional malignancies, laboratory abnormalities, or psychiatric illness that in the opinion of the investigator would interfere with the patient's safety or compliance while on trial
• Severe infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 4 weeks prior to enrollment

Sponsors & Collaborators

• Mamta Parikh: lead
• Karyopharm Therapeutics Inc: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; selinexor

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Leslie Garcia
• Organization: University of California, Davis

lesgarcia@ucdavis.edu

916-734-0156

Study Officials

• Mamta Parikh

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 23, 2021
• Study Start: April 8, 2021
• Primary Completion: January 4, 2024
• Study Completion: February 13, 2024
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Locations

US (1)