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Extensive Stage Lung Small Cell CarcinomaPhase 1NCT05353439

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

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Extensive Stage Lung Small Cell Carcinoma and Limited Stage Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 15 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
15 sitesUnited States
Study dates
27 Jul 2022to 13 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with relapse at study entry with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and with prior therapy with platinum doublet. Patients with extensive stage disease should have received chemo-immunotherapy. Both platinum-sensitive and platinum-resistant patients will be included
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with tazemetostat and topotecan in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 70%)
  • Leukocytes >= 3000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
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  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
  • Total bilirubin =< 1.5 institutional upper limit of normal (ULN) OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 × ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Creatinine =< 1.5 institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
  • Note: Creatinine clearance (CrCl) should be calculated per institutional standard. Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated (a)PTT =< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load (CD4 count of greater than 250 cells/mcL) within 6 months are eligible for this trial. They must not be receiving prophylactic therapy for an opportunistic infection
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if they are symptomatically stable while off steroid therapy for a minimum of 7 days
  • Patients should be class 2B or better on the New York Heart Association Functional Classification
  • Ability to understand and the willingness to sign a written informed consent document
  • The effects of pembrolizumab and tazemetostat on the developing human fetus are unknown. For this reason and because monoclonal antibodies, EZH2 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment and for 6 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study treatment administration

Who cannot join

  • Patients who have had chemotherapy, immune checkpoint inhibitors, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  • Note: Patients who have had palliative radiotherapy may be included as long as they have recovered from any radiotherapy related adverse events (allow at least 3 days between radiotherapy completion and study treatment)
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1).
  • Note: Patients with =< grade 2 neuropathy or =< grade 2 alopecia are an exception to this criterion and may qualify for the study
  • Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Untreated immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
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  • Patients who are receiving any other investigational agents
  • Patients with symptomatic brain metastasis are not eligible due to their extremely poor prognosis and since it is unclear whether the investigational agent penetrates the blood-brain barrier. However, subjects who have had treatment for their brain metastasis and are symptomatically stable while off steroid therapy for a minimum of 7 days may be enrolled. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab and tazemetostat or other agents used in study
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Patients with uncontrolled intercurrent illness but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because pembrolizumab as a monoclonal antibody, and tazemetostat as a EZH2 inhibitor may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab or tazemetostat, breastfeeding should be discontinued if the mother is treated with these agents and for 1 week after the last dose of tazemetostat. These potential risks may also apply to other agents used in this study
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C
  • Has received a live vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
  • Has thrombocytopenia, neutropenia, or anemia of grade >= 3 (per Common Terminology Criteria for Adverse Events [CTCAE] 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
  • Has abnormalities known to be associated with MDS (e.g. del 5q, chromosome [chr] 7 abnormality [abn]) and myeloproliferative neoplasm (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing
  • Has a prior history of T-cell lymphoblastic lymphoma (T-LBL), T-cell acute leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL)

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • NCI - Center for Cancer Research

    Bethesda, Maryland, 20892

  • Northwestern University

    Chicago, Illinois, 60611

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Keck Medicine of USC Koreatown

    Los Angeles, California, 90020

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Pembrolizumab, Tazemetostat Hydrobromide
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • PembrolizumabBiological

    Also called BCD-201, GME 751, GME751, Keytruda

    Given IV

  • Tazemetostat HydrobromideDrug

    Also called EPZ-6438 Monohydrobromide, Tazemetostat Monohydrobromide, TAZVERIK

    Given PO

  • Topotecan HydrochlorideDrug

    Also called Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride

    Given IV

Study groups in NCT05353439
Study groupRoleWhat they receive
Treatment (tazemetostat, pembrolizumab, topotecan)ExperimentalPatients receive tazemetostat PO BID for 7 days prior to cycle 1 and then on days 1-21 of each cycle, pembrolizumab 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 CT scan throughout the study and undergo biopsy and collection of blood on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Pembrolizumab; Drug: Tazemetostat Hydrobromide; Drug: Topotecan Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (dose-escalation cohort)

    Measured: Up to 21 days (cycle 1)

  2. Incidence of adverse events (expansion cohort)

    Will be evaluated in more detail by reporting the adverse events noted, by type and grade, for the patients in the expansion cohort.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Overall response rate

    Will be estimated based on patients evaluable for response and will be presented along with a 95% confidence interval.

    Measured: Up to 3 years

  2. Progression-free survival

    Will be estimated using the Kaplan-Meier method, resulting in median survival times with 95% confidence interval.

    Measured: From the on-study date until the date of progression or death without progression, assessed up to 3 years

  3. Overall survival

    Will be estimated using the Kaplan-Meier method, resulting in median survival times with 95% confidence interval.

    Measured: From the on-study date until the date of death or last follow-up, assessed up to 3 years

  4. Duration of response

    Will be estimated using the Kaplan-Meier method, resulting in median survival times with 95% confidence interval.

    Measured: From the first date of response to the date of progression, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2022
  2. Study start27 Jul 2022
  3. Primary completion11 Feb 2026
  4. Study completion13 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05353439
Sponsor's protocol ID
NCI-2022-03215
Other IDs
NCI-2022-03215, 22-C-0005, 10445, 10445
Status last verified
Mar 2026
First submitted
23 Apr 2022
Last updated
13 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Extensive Stage Lung Small Cell Carcinoma and Limited Stage Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (dose-escalation cohort) (time frame: Up to 21 days (cycle 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05353439.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.

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