Study of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Advanced Solid Malignancies (FAK-PD1)
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)
2 other identifiers
interventional
59
1 country
5
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2017
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 20, 2016
CompletedFirst Posted
Study publicly available on registry
May 2, 2016
CompletedStudy Start
First participant enrolled
July 4, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2021
CompletedMarch 19, 2018
March 1, 2018
1.8 years
April 20, 2016
March 16, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Adverse events (AEs) using CTCAE v4.03 (to determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD))
Evaluate the tolerability profile and optimal dose of defactinib in combination with pembrolizumab, using CTCAE v4.03 Adverse Event recording.
6 months
Secondary Outcomes (5)
Objective response rate (ORR), using best objective response by irRECIST
3 years
Duration of response (DoR)
3 years
Progression free survival (PFS)
3 years
Change in FAK Y397 phosphorylation
2 weeks
Change in immune cell infiltrate
2 weeks
Study Arms (4)
Dose - escalation
EXPERIMENTALDoes-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
Pancreatic
EXPERIMENTALPancreatic 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
NSCLC
EXPERIMENTALNSCLC 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.
Mesothelioma
EXPERIMENTALMesothelioma 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.
Interventions
cross reference with arm/group descriptions
cross reference with arm/group descriptions
Eligibility Criteria
You may qualify if:
- 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
- +10 more criteria
You may not qualify if:
- 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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NHS Greater Glasgow and Clydelead
- University of Glasgowcollaborator
- Cancer Research UKcollaborator
- Merck Sharp & Dohme LLCcollaborator
- Verastem, Inc.collaborator
- University of Edinburghcollaborator
- University of Southamptoncollaborator
- University of Leicestercollaborator
- Queen's University, Belfastcollaborator
Study Sites (5)
Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road
Belfast, BT9 7BL, United Kingdom
Edinburgh Cancer Research Centre, Western General Hospital
Edinburgh, EH4 2XR, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary
Leicester, LE2 7LX, United Kingdom
Cancer Research UK Centre, Southampton University Hospitals and University of Southampton
Southampton, SO16 6YD, United Kingdom
Related Publications (1)
Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.
PMID: 37598000DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- 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
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 20, 2016
First Posted
May 2, 2016
Study Start
July 4, 2017
Primary Completion
May 1, 2019
Study Completion
December 1, 2021
Last Updated
March 19, 2018
Record last verified: 2018-03
Data Sharing
- IPD Sharing
- Will not share