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Non-small Cell Lung CancerPhase 2KEYNOTE B36NCT04892472

EF-36/Keynote B36: A Pilot, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Pembrolizumab for First Line Treatment of Advanced or Metastatic Non-small Cell Lung Cancer

A Phase 2 study testing NovoTTF-200T and Pembrolizumab (MK-3475) 200 mg in people with Non-small Cell Lung Cancer, run by NovoCure GmbH at 24 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a multicenter, randomized, open-label study of Tumor Treating Fields (TTFields) at 150 kHz to the thorax using the NovoTTF-200T System with IV pembrolizumab in subjects previously untreated for advanced or metastatic, PD-L1 positive non-small cell lung cancer (NSCLC). Read more about this study

Who is it for?
Ages 22 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
NovoTTF-200T and Pembrolizumab (MK-3475) 200 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
24 sitesUnited States
Study dates
12 Jul 2021to 10 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

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

Who may be able to join

  • Histologically or cytologically confirmed diagnosis of stage III or metastatic NSCLC without EGFR sensitizing mutation or ALK translocation
  • Age ≥ 22 years
  • Have a PD-L1 positive (TPS≥1%) tumor by local laboratory assessment
  • Have evaluable (measureable or non-measureable) disease in thorax per RECIST 1.1
  • ECOG performance status of 0 to 1
  • Have not received prior treatments for metastatic or current advanced NSCLC. Palliative treatment is allowed and subjects who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease are eligible if therapy completed at least 12 months prior to the development of metastatic or current advanced disease.
  • Life expectancy of at least 3 months
  • Able to operate the NovoTTF-200T device

Who cannot join

  • Has known active or untreated CNS metastases and/or carcinomatous meningitis
  • Has an EGFR sensitizing mutation and/ or ALK translocation
  • Can be treated with curative intent with either surgical resection and/or chemoradiation
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agent directed to another stimulatory or co-inhibitory T cell receptor within the past 12 months
  • Has received prior systemic anti-cancer therapy for metastatic or current advanced NSCLC (palliative radiotherapy is allowed)
  • Being unable to operate the NovoTTF-200T device independently or with the help of a caregiver
Show all 9Show fewer
  • Pregnancy or breastfeeding
  • Received live vaccine in the past 30 days or had major surgery in the last 3 weeks
  • Is expected to require any other form of systemic or localized antineoplastic therapy while on study

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • Central Alabama Research

    Birmingham, Alabama, 35209

  • Aultman Hospital

    Canton, Ohio, 44710

  • Gabrail Cancer Research Center

    Canton, Ohio, 44718

  • Oncology Specialists of Charlotte

    Charlotte, North Carolina, 28210

  • University of Illinois Hospital and Health Sciences System

    Chicago, Illinois, 60612

  • UCHealth Memorial Hospital

    Colorado Springs, Colorado, 80909

  • Texas Oncology - Sammons Cancer Center

    Dallas, Texas, 75246

  • Saint Elizabeth Healthcare

    Edgewood, Kentucky, 41017

  • Arnot Ogen Medical Center - Falck Cancer Center

    Elmira, New York, 14905

  • Michigan Center of Medical Research

    Farmington Hills, Michigan, 48334

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Palo Verde Cancer Specialists

    Glendale, Arizona, 85304

  • : The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Franciscan St. Francis Health Indianapolis

    Indianapolis, Indiana, 46237

  • Tennessee Cancer Specialists

    Knoxville, Tennessee, 37909

  • Cancer Care of North Florida

    Lake City, Florida, 32024

  • OptumCare Cancer Care

    Las Vegas, Nevada, 89102

  • Baptist Health Oncology Research

    Lexington, Kentucky, 40503

  • Cancer Partners of Nebraska

    Lincoln, Nebraska, 68510

  • Long Beach Memorial Medical Center

    Long Beach, California, 90806

  • Miami Cancer Insititute - Baptist Health South Florida

    Miami, Florida, 33716

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Cancer and Leukemia Center

    Sterling Heights, Michigan, 48314

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

This is a multicenter, randomized, open-label study of Tumor Treating Fields (TTFields) at 150 kHz to the thorax using the NovoTTF-200T System with IV pembrolizumab in subjects previously untreated for advanced or metastatic, PD-L1 positive non-small cell lung cancer (NSCLC). The primary objective is to evaluate the progression-free survival (PFS) by RECIST 1.1 in subjects with TPS ≥1 percent, 1L metastatic/current advanced NSCLC treated with TTFields concomitant with pembrolizumab compared to those treated with pembrolizumab alone.

The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Read the detailed description

TTFields have demonstrated significant activity in vitro and in NSCLC pre-clinical models, both as a single modality treatment and concomitant with chemotherapies and PD-1 inhibitors. TTFields have demonstrated synergistic activity when administered alongside taxanes; while TTFields used concomitantly with PD-1 inhibition have shown additive effects.

In a pilot study, 42 advanced stage NSCLC patients, who had tumor progression after at least one line of prior chemotherapy, received pemetrexed together with TTFields (150 kHz) applied to the chest and upper abdomen until disease progression. The combination was well tolerated and the only device-related adverse event was mild to moderate contact dermatitis. Efficacy endpoints were remarkably high compared to historical data for pemetrexed alone.

Preclinical models have been used to assess the potency of TTFields concomitant with checkpoint inhibition. In an in vivo experiment, C57Bl/6 mice had LLC-1 cells injected directly into the lungs. TTFields were applied to the mouse lungs for 7 days in parallel to I.P. injections of anti-PD-1. Concomitant TTFields and anti-PD-1 treatments led to a significant decrease in tumor volume compared to control mice and to mice treated with anti-PD-1 alone. The concomitant treatments also resulted in an increase in the percentage of tumor-infiltrating leukocytes (CD45+). Specifically, there was a significantly higher frequency of macrophages (CD45+/CD11b+/F4/80+) and dendritic cells (CD45+/CD11c+) in tumors from mice that were concomitantly treated with TTFields and anti-PD-1. Concomitant therapy upregulated PD-1 expression on macrophages and dendritic cells in mice, suggesting an adaptive immune response to control the inflammation caused by the treatment. Additionally, cytotoxic T-cells isolated from tumors treated with TTFields and anti-PD-1 demonstrated increased production of IFN-γ. Overall, these findings imply that concomitant TTFields and anti-PD-1 therapy enhanced the immune response, which led to better management of the tumor.

The study will enroll 100 patients, whose tumors are classified as TPS>1% and in whom EGFR or ALK-directed therapy is not indicated, for examination of the effectiveness and safety of TTFields concomitant with pembrolizumab.

In addition, all patients must meet all eligibility criteria.

After a Screening Phase of up to 28 days, subjects will be enrolled to receive TTFields (150 kHz) to the thorax using the NovoTTF-200T device for an average of 18 hours a day concomitant with pembrolizumab 200 mg IV every 3 weeks, or pembrolizumab alone. Each subject will participate in the study for approximately 2 years from the time the subject signs the Informed Consent Form (ICF) through the final contact.

Treatment with TTFields and pembrolizumab will continue for 24 months (TTFields) and until either: (1) 35 study treatments have been administered (pembrolizumab), (2) there is documented disease progression (per iRECIST criteria), (3) unacceptable adverse event(s), (4) intercurrent illness that prevents further administration of treatment, (5) investigator's decision to withdraw the subject, (6) subject withdraws consent, (7) pregnancy of the subject, (8) non-compliance with study treatment or procedure requirements, or (9) administrative/Sponsor decisions.

In case of discontinuation of either of the study treatments due to reasons other than disease progression, the remaining treatment should continue until disease progression or 24 months (TTFields) / 35 cycles (pembrolizumab).

If an alternative anticancer therapy is initiated, the patient will be removed from the study.

Subjects who discontinue all study treatments prior to disease progression will be monitored for disease status in the Observation Phase until: (1) disease progression is confirmed by the site, (2) a non-study cancer treatment is initiated, (3) consent is withdrawn, or (4) the subject is lost to follow-up. Subjects will have post-treatment monthly follow-up by telephone for disease status until death, withdrawing consent, becoming lost to follow-up, or end of the study.

Being tested
NovoTTF-200T, Pembrolizumab (MK-3475) 200 mg
Keywords
Non-small cell lung cancer, NSCLC, Advanced non-small cell lung cancer, Metastatic non-small cell lung cancer, Immunotherapy, PDL-1 positive, Treatment, Minimal toxicity, TTFields, Tumor Treating Fields, Novocure, Pembrolizumab, Merck
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • NovoTTF-200TDevice

    All patients enrolled in this group will receive TTFields treatment, delivered for at an average of least 18 hours a day using NovoTTF-200T concomitant with pembrolizumab, a standard immunotherapy agent, which is delivered intravenously.

  • Pembrolizumab (MK-3475) 200 mgDrug

    Pembrolizumab (MK-3475) 200 mg every 3 weeks (Q3W)

Study groups in NCT04892472
Study groupRoleWhat they receive
Arm 1: Treatment GroupExperimentalPembrolizumab (MK-3475) and TTFields
Receives: Device: NovoTTF-200T; Drug: Pembrolizumab (MK-3475) 200 mg
Arm 2: Control GroupExperimentalPembrolizumab (MK-3475)
Receives: Drug: Pembrolizumab (MK-3475) 200 mg

What is being measured

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

  1. Progression Free Survival

    PFS will be measured from the date of enrollment to date of progression (in months) based on RECIST 1.1 criteria. The analysis will include stratification by PD-L1 expression, TPS≥1-49% and TPS≥50%, as a secondary outcome.

    Measured: 24 months

Secondary outcomes (5)

  1. Overall survival (OS)

    Survival will be measured from date of enrollment until date of death. The analysis will include patients with PD-L1 expression TPS≥1-49 percent and TPS≥50 percent

    Measured: 24 months

  2. Objective Response Rate (ORR)

    Percentage of patients who have a partial or complete response to therapy based on RECIST 1.1 criteria

    Measured: 24 months

  3. Duration of response (DOR)

    The analysis will be defined as the time from response to progression/death (P/D) based on RECIST 1.1 criteria

    Measured: 24 months

  4. Disease control rate (DCR)

    Will be defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response (CR), partial response (PR), and stable disease (SD) by RECIST 1.1 at 18 weeks

    Measured: 18 weeks

  5. Safety and Tolerability: adverse events (AEs)

    Will be defined as the incidence, frequency and severity of adverse events (AEs) noted in patients treated.

    Measured: 24 months

Timeline

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

  1. First posted19 May 2021
  2. Study start12 Jul 2021
  3. Primary completion10 Jan 2025
  4. Study completion10 Jan 2025

Why it stopped: Phase 2 study terminated due to insufficient enrollment and was not based on safety concerns. Novocure is enrolling a new Phase 3 study of TTFields as a first line treatment for advanced/metastatic NSCLC (NCT06216301).

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04892472
Sponsor's protocol ID
EF- 36
Other IDs
KEYNOTE-B36
Acronym
KEYNOTE B36
Status last verified
Apr 2025
First submitted
13 May 2021
Last updated
23 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Undecided

Publications

  • Lee SX, Wong ET, Swanson KD. Mitosis Interference of Cancer Cells by NovoTTF-100A Causes Decreased Cellular Viability. Cancer Res. 2013;73; 709. http://cancerres.aacrjournals.org/content/73/8%7B_%7DSupplement/709.abstract.

  • Bomzon Z, Urman N, Wenger C, et al. Transducer array layout optimization for treating lung-based tumors with TTFields. J Clin Oncol. 2015;33(suppl; abstr e18503). http://meetinglibrary.asco.org/content/147908-156.

  • Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.

    PubMed 23891283

  • Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.

    PubMed 17551011

  • Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.

    PubMed 15126372

  • Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046.

    PubMed 26658786

  • Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9.

    PubMed 21548832

  • Mun EJ, Babiker HM, Weinberg U, Kirson ED, Von Hoff DD. Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clin Cancer Res. 2018 Jan 15;24(2):266-275. doi: 10.1158/1078-0432.CCR-17-1117. Epub 2017 Aug 1.

    PubMed 28765323

  • Giladi M, Weinberg U, Schneiderman RS, Porat Y, Munster M, Voloshin T, Blatt R, Cahal S, Itzhaki A, Onn A, Kirson ED, Palti Y. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo. Semin Oncol. 2014 Oct;41 Suppl 6:S35-41. doi: 10.1053/j.seminoncol.2014.09.006. Epub 2014 Sep 8.

    PubMed 25213867

  • Voloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, Palti Y. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy. Cancer Immunol Immunother. 2020 Jul;69(7):1191-1204. doi: 10.1007/s00262-020-02534-7. Epub 2020 Mar 6.

    PubMed 32144446

  • Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.

    PubMed 19387848

  • Bomzon Z, Urman N, Wenger C, Giladi M, Weinberg U, Wasserman Y, Kirson ED, Miranda PC, Palti Y. Modelling Tumor Treating Fields for the treatment of lung-based tumors. Annu Int Conf IEEE Eng Med Biol Soc. 2015;2015:6888-91. doi: 10.1109/EMBC.2015.7319976.

    PubMed 26737876

  • Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.

    PubMed 22608262

  • Kirson ED, Schneiderman RS, Dbaly V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys. 2009 Jan 8;9:1. doi: 10.1186/1756-6649-9-1.

    PubMed 19133110

  • Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

    PubMed 29260225

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NovoTTF-200T and Pembrolizumab (MK-3475) 200 mg in people with Non-small Cell Lung Cancer, run by NovoCure GmbH at 24 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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: Phase 2 study terminated due to insufficient enrollment and was not based on safety concerns. Novocure is enrolling a new Phase 3 study of TTFields as a first line treatment for advanced/metastatic NSCLC (NCT06216301).). Results are not available in the source record.

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?

Progression Free Survival (time frame: 24 months). 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 NCT04892472, which also lists 23 linked publications.

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 23 Apr 2025.

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