NCT05353439

Testing of Tazemetostat in Combination With Topotecan and Pembrolizumab in Patients With Recurrent Small Cell Lung Cancer

Phase I Dose Escalation and Expansion Study of Tazemetostat in Combination With Topotecan and Pembrolizumab in Recurrent Small Cell Lung Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of tazemetostat in combination with topotecan and pembrolizumab in treating patients with small cell lung cancer that has come back after a period of improvement (recurrent). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 tazemetostat in combination with topotecan and pembrolizumab may shrink or stabilize recurrent small cell lung cancer.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of tazemetostat hydrobromide (tazemetostat) in combination with topotecan hydrochloride (topotecan) and pembrolizumab in patients with recurrent extensive stage (ES)-small cell lung cancer (SCLC), by reviewing dose-limiting toxicities (DLTs) in cycle 1 (21 days). (Dose-Escalation Cohort) II. To select the recommended phase II dose (RP2D) for a combination of tazemetostat, topotecan and pembrolizumab, based on pharmacodynamic (PD) parameters as well as overall efficacy and tolerability. (Dose-Escalation Cohort) III. To evaluate safety and tolerability of tazemetostat in combination with topotecan and pembrolizumab. (Expansion Cohort) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine in a very preliminary fashion, the efficacy of a combination of tazemetostat, topotecan and pembrolizumab in recurrent ES-SCLC by assessing overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to ribonucleic acid (RNA) sequencing (RNA-Seq). II. To assess modulation of EZH2 targets including SLFN11 and MHC among others. III. To identify potential predictive biomarkers of response. IV. To identify mechanisms of drug sensitivity and resistance using deoxyribonucleic acid (DNA)- and RNA-based assessment platforms. V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. VI. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank) at Nationwide Children's Hospital. VII. To characterize circulating cell-free DNA (cfDNA). OUTLINE: This is a dose-escalation study of tazemetostat followed by a dose-expansion study. Patients receive tazemetostat orally (PO) twice daily (BID) for 7 days prior to cycle 1 and then on days 1-21 of each cycle, pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle, and topotecan IV over 30 minutes on days 1-3 or days 1-5 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan throughout the study and undergo biopsy and collection of blood on study. After completion of study treatment, patients are followed every 3 months after removal from study treatment until study closure or death, whichever occurs first.

Conditions

• Extensive Stage Lung Small Cell Carcinoma
• Limited Stage Lung Small Cell Carcinoma
• Platinum-Resistant Lung Small Cell Carcinoma
• Platinum-Sensitive Lung Small Cell Carcinoma
• Recurrent Extensive Stage Lung Small Cell Carcinoma
• Recurrent Lung Small Cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Computed Tomography	Undergo CT scan
BIOLOGICAL	Pembrolizumab	Given IV
DRUG	Tazemetostat Hydrobromide	Given PO
DRUG	Topotecan Hydrochloride	Given IV

Timeline

• Start date: 2022-07-27
• Primary completion: 2026-02-11
• Completion: 2027-03-13
• First posted: 2022-04-29
• Last updated: 2026-04-13

Locations

15 sites across 1 country: United States

Regulatory

• FDA-regulated drug study