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Study of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Advanced Solid Malignancies (FAK-PD1)

This study is currently recruiting participants.
Verified July 2017 by NHS Greater Glasgow and Clyde
Sponsor:
ClinicalTrials.gov Identifier:
NCT02758587
First Posted: May 2, 2016
Last Update Posted: August 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
University of Glasgow
Cancer Research UK
Merck Sharp & Dohme Corp.
Verastem, Inc.
University of Edinburgh
University of Southampton
University of Leicester
Queen's University, Belfast
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde
  Purpose
This study will explore whether defactinib (a FAK inhibitor) can be safely and tolerably combined with pembrolizumab (a PD-1 inhibitor) and will look for early indications of improved anticancer immunotherapy. It will focus on three key cancers, all in clear need of improved therapies - NSCLC, pancreatic cancer and mesothelioma.

Condition Intervention Phase
Carcinoma, Non-small-cell Lung Mesothelioma Pancreatic Neoplasms Drug: Defactinib Drug: Pembrolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIA Study to Assess Safety, Tolerability and Preliminary Activity of the Combination of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Patients With Advanced Solid Malignancies (FAK-PD1)

Resource links provided by NLM:


Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:
  • Adverse events (AEs) using CTCAE v4.03 (to determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD)) [ Time Frame: 6 months ]
    Evaluate the tolerability profile and optimal dose of defactinib in combination with pembrolizumab, using CTCAE v4.03 Adverse Event recording.


Secondary Outcome Measures:
  • Objective response rate (ORR), using best objective response by irRECIST [ Time Frame: 3 years ]
    Evaluate the response rate, by irRECIST, of the combination of defactinib and pembrolizumab in patients with advanced solid malignancies.

  • Duration of response (DoR) [ Time Frame: 3 years ]
    Evaluate the duration of responses, by irRECIST, of the combination of defactinib and pembrolizumab in patients with advanced solid malignancies. Duration will be measured from the first scan showing radiological response (CR or PR), until (irRECIST confirmed) progression.

  • Progression free survival (PFS) using irRECIST [ Time Frame: 3 years ]
    Evaluate progression free survival of the combination of defactinib and pembrolizumab in patients with advanced solid malignancies. Duration will be measured from enrolment, until (irRECIST confirmed) progression.

  • Overall survival [ Time Frame: 3 years ]
    Evaluate overall survival of the combination of defactinib and pembrolizumab in patients with advanced solid malignancies. Duration will be measured from enrolment, until date of death.

  • Change in FAK Y397 phosphorylation [ Time Frame: 2 weeks ]
    change in FAK Y397 phosphorylation between baseline biopsy and a repeat biopsy afer 2 weeks of therapy

  • Change in immune cell infiltrate [ Time Frame: 2 weeks ]
    change in immune cell infiltrate between baseline biopsy and a repeat biopsy after 2 weeks of therapy


Estimated Enrollment: 59
Actual Study Start Date: July 4, 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose - escalation

Does-escalation in an "all-comers" phase I population, with treatment-refractory advanced solid malignancies, unselected by tumour type. Two cohorts of up to evaluable 6 patients in each:

  • Cohort 1: 200mg (IV) pembrolizumab every 3 weeks; plus 200mg (oral) defactinib twice daily
  • Cohort 2: 200mg (IV) pembrolizumab every 3 weeks; plus 400mg (oral) defactinib twice daily

Interventions:

  • Drug: Defactinib
  • Drug: Pembrolizumab
Drug: Defactinib
cross reference with arm/group descriptions
Other Name: VS-6063
Drug: Pembrolizumab
cross reference with arm/group descriptions
Other Name: Keytruda and MK-3475
Experimental: Pancreatic
Pancreatic expansion for response assessment (single arm). Optional paired biopsies prior to treatment and after 14 days of treatment. All would have concurrent therapy with pembrolizumab + defactinib (VS-6063) from the start (c.f. NSCLC & mesothelioma expansions below). 15 evaluable patients with an interim futility assessment for clinical response and tolerability when data available from 6
Drug: Defactinib
cross reference with arm/group descriptions
Other Name: VS-6063
Drug: Pembrolizumab
cross reference with arm/group descriptions
Other Name: Keytruda and MK-3475
Experimental: NSCLC
NSCLC paired-biopsy expansion for tissue biomarkers. Mandatory biopsies prior to treatment and after around 14 days of treatment. 1:1 randomised split of patients having their mandatory on-treatment biopsy after concurrent therapy, or after a defactinib (VS-6063) monotherapy run-in. 16 evaluable patients with an interim futility assessment for clinical response and tolerability when data available from 11.
Drug: Defactinib
cross reference with arm/group descriptions
Other Name: VS-6063
Drug: Pembrolizumab
cross reference with arm/group descriptions
Other Name: Keytruda and MK-3475
Experimental: Mesothelioma
Mesothelioma paired-biopsy expansion for tissue biomarkers. Mandatory biopsies prior to treatment and around 14 days of treatment. 1:1 randomised split of patients having thier on-treatment biopsy after concurrent therapy, or after defactinib (VS-6063) monotherapy run-in. 16 evaluable patients with an interim futility assessment for clinical response and tolerability when data available from 11.
Drug: Defactinib
cross reference with arm/group descriptions
Other Name: VS-6063
Drug: Pembrolizumab
cross reference with arm/group descriptions
Other Name: Keytruda and MK-3475

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All Patients:

  • Informed, written consent
  • Male or female, aged 18 years or older at the time consent is given
  • ECOG performance status 0 or 1, with no deterioration over the previous 2 weeks
  • Life expectancy of at least 3 months
  • Measurable disease according to irRECIST criteria, with at least one measurable lesion that has objectively progressed since (or on) any previous therapy
  • Adequate bone marrow, liver and renal function on blood investigations within 7 days prior to treatment initiation
  • Patients must have been offered all appropriate standard-of-care treatments (or all those indicated before anti-PD-1/PD-L1 therapy, if licensed)
  • Patients must agree to use adequate contraceptive measures for the course of the study through 120 days after the last dose of study medication
  • Women of child-bearing potential must have a negative pregnancy test within 72 hours prior to start of dosing
  • Consent to supply any available archival tissue

Dose escalation (Phase I):

  • Pathological diagnosis of any advanced solid tumour type, with confirmation that a tissue sample (core biopsy or resected specimen) is available

Pancreatic expansion (Phase IIa):

  • Pathological diagnosis of pancreatic ductal adenocarcinoma with confirmation that a tissue sample (core biopsy or resected specimen) is available

NSCLC expansion (Phase IIa):

  • Pathological diagnosis of non-small cell lung cancer (NSCLC)
  • Lesion suitable for repeat biopsy
  • Baseline biopsy containing tumour material during eligibility
  • Consent for paired biopsies on study

Mesothelioma expansion (Phase IIa):

  • Pathological diagnosis of mesothelioma
  • Lesion suitable for repeat biopsy
  • Baseline biopsy containing tumour material during eligibility
  • Consent for paired biopsies on study

Exclusion Criteria:

All patients:

  • An additional invasive cancer in the last 5 years (other than treated and controlled localised non-melanoma skin cancer or cervical carcinoma-in-situ, or indolent prostate cancer that has been stable for > 1 year)
  • Any central nervous system metastases unless treated and asymptomatic, as well as stable on imaging and not requiring steroids in the preceding 4 weeks
  • Any interventional studies, systemic cancer therapies or monoclonal antibodies in the preceding 4 weeks (6 weeks for mitomycin C and nitrosureas)
  • Any live vaccines in the preceding 4 weeks
  • Systemic immunosuppressive agents in the preceding 2 weeks. Immunosuppressive agents include steroids such as prednisolone (doses ≥ 15 mg daily) or dexamethasone (doses ≥ 2 mg daily).

Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc) is not considered a form of systemic treatment

  • Diagnosis of immunodeficiency
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Known interstitial lung disease or active, non-infectious pneumonitis
  • Known history of Tuberculosis (TB), Human Immunodeficiency Virus (HIV) or active Hepatitis B or C
  • Other severe or uncontrolled systemic diseases (e.g. uncontrolled hypertension, recent myocardial infarction, organ failure or active infection)
  • Baseline (non-laboratory) toxicities greater than grade 1 (CTCAE v4.03) despite optimal supportive therapy, including fatigue, anorexia, nausea or diarrhoea, but with the exception of alopecia
  • Pregnancy or lactation
  • Limited ability to swallow or absorb oral medications
  • Hypersensitivity to defactinib (VS-6063), pembrolizumab or excipients (including L-histidine, L-histidine hydrochloride monohydrate, sucrose or polysorbate 80)
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in is not in the best interest of the subject to participate, in the opinion of the treating investigator
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02758587


Contacts
Contact: Dawn Currie 00 44 141 301 7194 dawn.currie@glasgow.ac.uk

Locations
United Kingdom
Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road Not yet recruiting
Belfast, United Kingdom, BT9 7BL
Contact: Melanie Morris    00 44 28 9063 8468    melanie.morris@belfasttrust.hscni.net   
Principal Investigator: Vicky Coyle, Dr         
Edinburgh Cancer Research Centre, Western General Hospital Recruiting
Edinburgh, United Kingdom, EH4 2XR
Contact: Olga Demyanov    00 44 131 537 2202    olga.demyanov@ed.ac.uk   
Principal Investigator: Stefan Symeonides, Dr         
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Jeff Evans       j.evans@beatson.gla.ac.uk   
Principal Investigator: Jeff Evans, Prof         
Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary Not yet recruiting
Leicester, United Kingdom, LE2 7LX
Contact: Dean Fennell       df132@leicester.ac.uk   
Principal Investigator: Dean Fennell, Prof         
Cancer Research UK Centre, Southampton University Hospitals and University of Southampton Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Christian Ottensmeier       c.h.ottensmeier@soton.ac.uk   
Principal Investigator: Christian Ottensmeier, Prof         
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
Cancer Research UK
Merck Sharp & Dohme Corp.
Verastem, Inc.
University of Edinburgh
University of Southampton
University of Leicester
Queen's University, Belfast
Investigators
Principal Investigator: Stefan Symeonides Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR
Principal Investigator: Jeff Evans Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN
Principal Investigator: Christian Ottensmeier Cancer Research UK Centre, Southampton University Hospitals and University of Southampton, Southampton SO16 6YD
Principal Investigator: Dean Fennell Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX
Principal Investigator: Vicky Coyle Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road, Belfast BT9 7BL
  More Information

Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT02758587     History of Changes
Other Study ID Numbers: GN15ON133
2015-003928-31 ( EudraCT Number )
First Submitted: April 20, 2016
First Posted: May 2, 2016
Last Update Posted: August 10, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Mesothelioma
Pembrolizumab
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents