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

NCT04892472 | Terminated Phase 2 FDA Drug FDA Device

• 2 other identifiers: EF- 36KEYNOTE-B36
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 24

Brief 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). 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.

Conditions

Non-small Cell Lung Cancer

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

Outcome Measures

Primary Outcomes (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.

  24 months

Secondary Outcomes (5)

• Overall survival (OS)

  24 months

• Objective Response Rate (ORR)

  24 months

• Duration of response (DOR)

  24 months

• Disease control rate (DCR)

  18 weeks

• Safety and Tolerability: adverse events (AEs)

  24 months

Study Arms (2)

Arm 1: Treatment Group

EXPERIMENTAL

Pembrolizumab (MK-3475) and TTFields

Device: NovoTTF-200T; Drug: Pembrolizumab (MK-3475) 200 mg

Arm 2: Control Group

EXPERIMENTAL

Pembrolizumab (MK-3475)

Drug: Pembrolizumab (MK-3475) 200 mg

Interventions

NovoTTF-200T DEVICE

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.

Arm 1: Treatment Group

Pembrolizumab (MK-3475) 200 mg DRUG

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

Arm 1: Treatment Group; Arm 2: Control Group

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• NovoCure GmbH: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (24)

Central Alabama Research

Birmingham, Alabama, 35209, United States

Location

Palo Verde Cancer Specialists

Glendale, Arizona, 85304, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

UCHealth Memorial Hospital

Colorado Springs, Colorado, 80909, United States

Location

Cancer Care of North Florida

Lake City, Florida, 32024, United States

Location

Miami Cancer Insititute - Baptist Health South Florida

Miami, Florida, 33716, United States

Location

University of Illinois Hospital and Health Sciences System

Chicago, Illinois, 60612, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

Franciscan St. Francis Health Indianapolis

Indianapolis, Indiana, 46237, United States

Location

Saint Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

Baptist Health Oncology Research

Lexington, Kentucky, 40503, United States

Location

Michigan Center of Medical Research

Farmington Hills, Michigan, 48334, United States

Location

Cancer and Leukemia Center

Sterling Heights, Michigan, 48314, United States

Location

Cancer Partners of Nebraska

Lincoln, Nebraska, 68510, United States

Location

OptumCare Cancer Care

Las Vegas, Nevada, 89102, United States

Location

Arnot Ogen Medical Center - Falck Cancer Center

Elmira, New York, 14905, United States

Location

Oncology Specialists of Charlotte

Charlotte, North Carolina, 28210, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Gabrail Cancer Research Center

Canton, Ohio, 44718, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

Texas Oncology - Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

: The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (23)

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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;81(3):445-450. doi:10.1016/j.lungcan.2013.06.025 17. Hanna N, Shepherd FA, Fossella F V, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589-1597. doi:10.1200/JCO.2004.08.163

  BACKGROUND

• 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.

  PMID: 17551011 RESULT

• 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.

  PMID: 15126372 RESULT

• 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.

  PMID: 26658786 RESULT

• 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.

  PMID: 21548832 RESULT

• 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.

  PMID: 28765323 RESULT

• 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.

  PMID: 25213867 RESULT

• 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.

  PMID: 32144446 RESULT

• 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.

  PMID: 19387848 RESULT

• 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.

  PMID: 26737876 RESULT

• 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.

  PMID: 22608262 RESULT

• 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.

  PMID: 19133110 RESULT

• 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.

  PMID: 29260225 RESULT

• Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, Toms SA, Honnorat J, Chen TC, Sroubek J, David C, Idbaih A, Easaw JC, Kim CY, Bruna J, Hottinger AF, Kew Y, Roth P, Desai R, Villano JL, Kirson ED, Ram Z, Stupp R. Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):495-504. doi: 10.1001/jamaoncol.2017.5082.

  PMID: 29392280 RESULT

• Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.

  PMID: 12860938 RESULT

• Ceresoli GL, Aerts JG, Dziadziuszko R, Ramlau R, Cedres S, van Meerbeeck JP, Mencoboni M, Planchard D, Chella A, Crino L, Krzakowski M, Russel J, Maconi A, Gianoncelli L, Grosso F. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1702-1709. doi: 10.1016/S1470-2045(19)30532-7. Epub 2019 Oct 15.

  PMID: 31628016 RESULT

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 RESULT

• Toms SA, Kim CY, Nicholas G, Ram Z. Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. J Neurooncol. 2019 Jan;141(2):467-473. doi: 10.1007/s11060-018-03057-z. Epub 2018 Dec 1.

  PMID: 30506499 RESULT

• Mrugala MM, Engelhard HH, Dinh Tran D, Kew Y, Cavaliere R, Villano JL, Annenelie Bota D, Rudnick J, Love Sumrall A, Zhu JJ, Butowski N. Clinical practice experience with NovoTTF-100A system for glioblastoma: The Patient Registry Dataset (PRiDe). Semin Oncol. 2014 Oct;41 Suppl 6:S4-S13. doi: 10.1053/j.seminoncol.2014.09.010. Epub 2014 Sep 16.

  PMID: 25213869 RESULT

• Kanner AA, Wong ET, Villano JL, Ram Z; EF-11 Investigators. Post Hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A system versus best physician's choice chemotherapy. Semin Oncol. 2014 Oct;41 Suppl 6:S25-34. doi: 10.1053/j.seminoncol.2014.09.008. Epub 2014 Sep 16.

  PMID: 25213871 RESULT

• Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.

  PMID: 28271869 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 19, 2021
• Study Start: July 12, 2021
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2025
• Last Updated: April 23, 2025

Record last verified: 2025-04

Locations

US (24)