Lung Cancer Clinical Trial

Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Pembrolizumab for Treatment of Advanced Non-small Cell Lung Cancer (NSCLC)

Summary

This is a multicenter, single arm, open-label study of Tumor Treating Fields (TTFields) at 150 kHz to the thorax using the NovoTTF-200T System concomitant with IV pembrolizumab in subjects previously untreated for their advanced or metastatic intrathoracic, PD-L1 positive non-small cell lung cancer (NSCLC). The primary objective is to evaluate the objective response rate (ORR) by RECIST 1.1 in subjects with TPS ≥1 percent.

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

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Full Description

TTFields have demonstrated significant activity in in-vitro and NSCLC pre-clinical models, both as a single modality treatment and in combination with chemotherapies and PD-1 inhibitors. With taxanes, TTFields have been demonstrated to act synergistically, while TTFields have been shown to be additive when combined with PD-1 inhibition.

In a pilot study of 42 patients with advanced NSCLC who had tumor progression after at least one line of prior chemotherapy, all participants 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.

The potency of TTFields combined with checkpoint inhibition has been investigated in pre-clinical models. In an in-vivo experiment, C57Bl/6 mice were injected directly into the lungs with LLC-1 cells. Application of TTFields to the mouse lungs was maintained for 7 days and parallel to the ongoing I.P. injection of anti-PD-1. The combined treatment of TTFields and anti-PD-1 led to a significant decrease in tumor volume as compared to control mice and to mice treated with anti-PD-1 alone. The combined treatment 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 DCs (CD45+/CD11c+) in tumors from mice that were concomitantly treated with TTFields and anti-PD-1. The PD-L1 expression levels of these cells were increased as compared to the control group suggesting an adaptive immune attempt to limit the inflammatory response elicited by the combined treatment. Compatibly, cytotoxic T-cells isolated from tumors treated with TTFields and anti-PD-1 demonstrated increased production of IFN-γ. 061

Taken together, these results suggest that the combination of TTFields and anti-PD-1 augmented the immune response resulting in improved tumor control.

The study will enroll 66 patients, whose tumors are classified as TPS>1% and in whom EGFR or ALK-directed therapy is not indicated, are projected to be enrolled in this study for examination of the effectiveness and safety of TTFields concomitant with pembrolizumab.

In addition, all patients must meet all eligibility criteria.

Subjects will be enrolled after a Screening Phase of up to 28 days to receive TTFields at 150 kHz to the thorax using the NovoTTF-200T System for at least 18 hours a day on average concomitant with pembrolizumab 200 mg IV every 3 weeks. 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed, newly diagnosed unresectable stage III or metastatic (M1a) intrathoracic NSCLC without EGFR sensitizing mutation or ALK translocation
Age ≥ 22 years
Have a PD-L1 positive (TPS≥1%) tumor by local laboratory assessment
Measurable disease by RECIST 1.1
ECOG performance status of 0 to 1
Have not received prior systemic treatments for NSCLC.
Life expectancy of at least 3 months
Able to operate the NovoTTF-200T system

Exclusion Criteria:

Has an extrathoracic metastasis (i.e. M component is M1b or M1c)
Has an EGFR sensitizing mutation and/ or ALK translocation
If Stage III, can be treated with curative intent with either surgical resection and/or chemoradiation
Has received prior systemic anti-cancer therapy or prior radiotherapy for NSCLC (palliative radiotherapy is allowed)
Being unable to operate the NovoTTF-200T device independently or with the help of a caregiver
Pregnancy or breastfeeding
Significant illnesses not associated with the primary disease
Implanted electronic devices (e.g. pacemaker) in the upper torso

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

66

Study ID:

NCT04892472

Recruitment Status:

Recruiting

Sponsor:

NovoCure GmbH

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There are 24 Locations for this study

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Central Alabama Research
Birmingham Alabama, 35209, United States More Info
Lorie Szymela
Contact
205-949-1907
[email protected]
Khaleel Ashraf, MD
Principal Investigator
Palo Verde Cancer Specialists
Glendale Arizona, 85304, United States More Info
Deepak Nayak
Contact
602-978-6255
[email protected]
Amol Rakkar, MD
Principal Investigator
Mayo Clinic
Phoenix Arizona, 85054, United States More Info
Clinical Trials Office
Contact
855-776-0015
Vinicius Ernani, MD
Principal Investigator
Long Beach Memorial Medical Center
Long Beach California, 90806, United States More Info
Laura Macias
Contact
562-933-7866
[email protected]
Nilesh Vora, MD
Principal Investigator
UCHealth Memorial Hospital
Colorado Springs Colorado, 80909, United States More Info
Alicia Deschaine
Contact
719-365-2406
[email protected]
Robert Hoyer, MD
Principal Investigator
Cancer Care of North Florida
Lake City Florida, 32024, United States More Info
Jessica Endsley
Contact
386-755-1655
[email protected]
Waseemulla Khan, MD
Principal Investigator
Miami Cancer Insititute - Baptist Health South Florida
Miami Florida, 33716, United States More Info
Juliet Rivero
Contact
786-527-8541
[email protected]
Rupesh Kotecha, MD
Principal Investigator
AdventHealth Orlando Research Institute
Orlando Florida, 32804, United States More Info
Alejandra Ricaurte
Contact
407-303-7456
[email protected]
Tarek Mekhail, MD
Principal Investigator
Parkview Research Center
Fort Wayne Indiana, 46845, United States More Info
Jon Lehrman
Contact
260-266-6633
[email protected]
Charles Vu, MD
Principal Investigator
Franciscan St. Francis Health Indianapolis
Indianapolis Indiana, 46237, United States More Info
Joyce Ogban
Contact
317-528-7060
[email protected]
Michael Eaton, MD
Principal Investigator
Saint Elizabeth Healthcare
Edgewood Kentucky, 41017, United States More Info
Colleen Darnell, MD
Principal Investigator
Baptist Health Oncology Research
Lexington Kentucky, 40503, United States More Info
Michael Mejia
Contact
859-260-6368
[email protected]
Firas Badin, MD
Principal Investigator
Central Maine Medical Center
Lewiston Maine, 04240, United States
Michigan Center of Medical Research
Farmington Hills Michigan, 48334, United States More Info
Julian Bailey, MD
Contact
248-747-4383
[email protected]
Savitha Balaraman, MD
Principal Investigator
Cancer and Leukemia Center
Sterling Heights Michigan, 48314, United States More Info
Julian Bailey, MD
Contact
248-747-4383
[email protected]
Savitha Balaraman, MD
Principal Investigator
OptumCare Cancer Care
Las Vegas Nevada, 89102, United States More Info
Christine Martinez
Contact
702-724-8787
[email protected]
John Ellerton, MD
Principal Investigator
Arnot Ogen Medical Center - Falck Cancer Center
Elmira New York, 14905, United States More Info
Christy Rumsey
Contact
607-271-3796
[email protected]
Serge Dauphin, MD
Principal Investigator
Oncology Specialists of Charlotte
Charlotte North Carolina, 28210, United States More Info
Justin Favaro, MD
Principal Investigator
Aultman Hospital
Canton Ohio, 44710, United States More Info
Carla Larch
Contact
330-363-7412
[email protected]
Raza Khan, MD
Principal Investigator
Gabrail Cancer Research Center
Canton Ohio, 44718, United States More Info
Carrie Smith
Contact
330-492-3345
[email protected]
Nashat Gabrail, MD
Principal Investigator
Lankenau Medical Center
Wynnewood Pennsylvania, 19096, United States More Info
Sandra Lyon, OCN
Contact
484-476-3494
[email protected]
Albert DeNittis, MD
Principal Investigator
Tennessee Cancer Specialists
Knoxville Tennessee, 37909, United States More Info
Kristi Simcox
Contact
865-934-2670
[email protected]
Richard T Lee, MD
Principal Investigator
Texas Oncology - Sammons Cancer Center
Dallas Texas, 75246, United States More Info
Jonathan Huntzinger
Contact
214-370-1942
[email protected]
Kartik Konduri, MD
Principal Investigator
: The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Aileen Chen
Contact
281-684-7350
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

66

Study ID:

NCT04892472

Recruitment Status:

Recruiting

Sponsor:


NovoCure GmbH

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