Study of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Advanced Solid Malignancies (FAK-PD1)
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ClinicalTrials.gov Identifier: NCT02758587 |
Recruitment Status : Unknown
Verified March 2018 by NHS Greater Glasgow and Clyde.
Recruitment status was: Recruiting
First Posted : May 2, 2016
Last Update Posted : March 19, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Carcinoma, Non-small-cell Lung Mesothelioma Pancreatic Neoplasms | Drug: Defactinib Drug: Pembrolizumab | Phase 1 Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 59 participants |
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) |
Actual Study Start Date : | July 4, 2017 |
Estimated Primary Completion Date : | May 2019 |
Estimated Study Completion Date : | December 2021 |

Arm | Intervention/treatment |
---|---|
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:
Interventions:
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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 |
- 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.
- 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) [ 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.
- 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

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, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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)
- Residual (non-laboratory) toxicities greater than grade 1 (CTCAE v4.03) from previous therapies 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
- Previous treatment with an anti-PD-1 or anti-PDL1 agent
- Previous severe or life-threatening skin adverse reaction with other immune-stimulatory anticancer agents
- Current solid organ transplant recipient

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
Contact: Dawn Currie | 00 44 141 301 7194 | dawn.currie@glasgow.ac.uk |
United Kingdom | |
Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road | Recruiting |
Belfast, United Kingdom, BT9 7BL | |
Contact: Melanie Morris 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 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 | 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 | Recruiting |
Southampton, United Kingdom, SO16 6YD | |
Contact: Christian Ottensmeier c.h.ottensmeier@soton.ac.uk | |
Principal Investigator: Christian Ottensmeier, Prof |
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 |
Responsible Party: | NHS Greater Glasgow and Clyde |
ClinicalTrials.gov Identifier: | NCT02758587 |
Other Study ID Numbers: |
GN15ON133 2015-003928-31 ( EudraCT Number ) |
First Posted: | May 2, 2016 Key Record Dates |
Last Update Posted: | March 19, 2018 |
Last Verified: | March 2018 |
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 |
Mesothelioma Carcinoma, Non-Small-Cell Lung Pancreatic Neoplasms Neoplasms Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms, Mesothelial Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site |
Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Digestive System Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents |