Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

NovoTTF-200T

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

Pembrolizumab (MK-3475) 200 mg

Kassie Balestrieri, PhD

Lorie Szymela

Khaleel Ashraf, MD

Deepak Nayak

Amol Rakkar, MD

Clinical Trials Office

Vinicius Ernani, MD

Laura Macias

Nilesh Vora, MD

Alicia Deschaine

Robert Hoyer, MD

Jessica Endsley

Waseemulla Khan, MD

Juliet Rivero

Rupesh Kotecha, MD

Lawrence Feldman, MD

Jon Lehrman

Charles Vu, MD

Joyce Ogban

Michael Eaton, MD

Amy Pajk

Colleen Darnell, MD

Michael Mejia

Firas Badin, MD

Julian Bailey, MD

Savitha Balaraman, MD

Haris Zahoor, MD, MS

Christine Martinez

John Ellerton, MD

Christy Rumsey

Serge Dauphin, MD

Joe Howe

Justin Favaro, MD

Carla Larch

Raza Khan, MD

Carrie Smith

Nashat Gabrail, MD

Sandra Lyon, OCN

Albert DeNittis, MD

Kristi Simcox

Richard T Lee, MD

Jonathan Huntzinger

Kartik Konduri, MD

Pablo B Lopez

Aileen Chen

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.

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.

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

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.

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

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

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

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

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

Merck Sharp & Dohme LLC

NovoCure GmbH

Symptoms and General Pathology

Neoplasm Metastasis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients receive three doses of NG-350A by intravenous infusion and a single dose of Pembrolizumab by intravenous infusion

NG-350A plus Pembrolizumab

Akamis Bio Ltd

David Park, MD

Christopher Lim

Lee Rosen, MD

Amy Whitaker

Guru Sonpavde, MD

Jennifer Louie

Mark O'Hara, MD

Yali Yang, PhD

Aung Naing, MD

Maria Maguire

Christian Ottensmeier, MD

Richard Cousins

Eileen Parkes, MD

This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-350A in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours.

Phase 1a will investigate NG-350A administration by intravenous (IV) infusion in combination with fixed-dose pembrolizumab in patients with metastatic or advanced tumours.

Phase 1b will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in Phase 1a.

Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY)

A Multicentre, Open-label, Non-randomized, Phase 1a/1b Study of NG-350A, a Tumour-selective Anti-CD40-expressing Adenoviral Vector, in Combination With Pembrolizumab in Patients With Metastatic or Advanced Epithelial Tumours

Assess the safety and tolerability of NG-350A in combination with pembrolizumab by review of adverse events including serious adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.

Akamis Bio

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	Non-small Cell ...	NovoTTF-200T Pembrolizumab (...	22 Years -	NovoCure Ltd.
Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY)	NCT05165433	Epithelial Tumo... Metastatic Canc...	NG-350A plus Pe...	18 Years -	Akamis Bio

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Every month we try and update this database with for merck cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for merck

Every month we try and update this database with for merck cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for merck cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.