Clinical Trials /

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

NCT04892472

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Pembrolizumab for Treatment of Advanced Non-small Cell Lung Cancer (NSCLC)
  • Official Title: EF-36/Keynote B36: A Pilot, Single Arm, Open-label Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Pembrolizumab for First Line Treatment of Advanced or Metastatic Intrathoracic Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: EF- 36
  • SECONDARY ID: KEYNOTE-B36
  • NCT ID: NCT04892472

Conditions

  • Non-small Cell Lung Cancer

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
Study ArmExperimentalPembrolizumab and TTFields

    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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:22 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Objective Response Rate (ORR)
    Time Frame:24 months
    Safety Issue:
    Description:ORR will be measured from the date of enrollment to date of progression (in months) based on RECIST 1.1 criteria. The analysis will include patients with PD-L1 expression TPS≥1-49 percent and TPS≥50 percent as a Secondary Outcome

    Secondary Outcome Measures

    Measure:Overall survival (OS)
    Time Frame:24 months
    Safety Issue:
    Description: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
    Measure:Progression Free Survival (PFS)
    Time Frame:24 months
    Safety Issue:
    Description:The analysis will be estimated proportions of patients who are progression-free based on the RECIST 1.1 criteria following the time of enrollment. The analysis will include patients with PD-L1 expression TPS≥1-49 percent and TPS≥50 percent
    Measure:Progression Free Survival at 6 months (PFS6)
    Time Frame:6 months
    Safety Issue:
    Description:The analysis will be estimated proportions of patients who are progression-free at 6 months based on the RECIST 1.1 criteria following the time of enrollment
    Measure:1-year survival rates
    Time Frame:12 months
    Safety Issue:
    Description:The analyses will be performed based on estimated proportions of patients who are alive at one year following enrollment
    Measure:Duration of response (DOR)
    Time Frame:24 months
    Safety Issue:
    Description:The analysis will be defined as the time from response to progression/death (P/D) based on RECIST 1.1 criteria
    Measure:Disease control rate (DCR)
    Time Frame:24 months
    Safety Issue:
    Description: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
    Measure:Safety and Tolerability: adverse events (AEs)
    Time Frame:24 months
    Safety Issue:
    Description:Will be defined as the incidence, frequency and severity of adverse events (AEs) noted in patients treated with TTFields concomitant with pembrolizumab, as well as their association with study treatments

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:NovoCure GmbH

    Trial 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

    Last Updated

    July 2, 2021