Ignite Creation Date:
2024-05-06 @ 4:09 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04892472
Status:
RECRUITING
Last Update Posted:
2023-10-06
First Post:
2021-05-13
Brief Title:
EF-36Keynote 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
Sponsor:
NovoCure GmbH
Organization:
NovoCure Ltd
Study Overview
Official Title:
EF-36Keynote 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
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KEYNOTE B36
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 11 in subjects with TPS 1 percent 1L metastaticcurrent 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
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
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 C57Bl6 mice had LLC-1 cells injected directly into the lungs TTFields were applied to the mouse lungs for 7 days in parallel to IP 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 CD45CD11bF480 and dendritic cells CD45CD11c 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 TPS1 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 events 4 intercurrent illness that prevents further administration of treatment 5 investigators 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 administrativeSponsor 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
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 C57Bl6 mice had LLC-1 cells injected directly into the lungs TTFields were applied to the mouse lungs for 7 days in parallel to IP 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 CD45CD11bF480 and dendritic cells CD45CD11c 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 TPS1 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 events 4 intercurrent illness that prevents further administration of treatment 5 investigators 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 administrativeSponsor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| KEYNOTE-B36 | OTHER | Merck Sharp Dohme Corp | None |