Carcinoma, Non-small-cell LungPhase 1/2NCT02758587
Study of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Advanced Solid Malignancies (FAK-PD1)
A Phase 1/2 study testing Defactinib and Pembrolizumab in people with Carcinoma, Non-small-cell Lung and Mesothelioma, run by NHS Greater Glasgow and Clyde at 5 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-small-cell Lung, Mesothelioma, Pancreatic Neoplasms
- What is being tested?
- Defactinib and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 4 Jul 2017to Dec 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 25Show fewer
- 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
Who cannot join
- 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).
Show all 20Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites, 5 recruiting
- Recruiting
Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road
Belfast, BT9 7BL
Melanie Morris, melanie.morris@belfasttrust.hscni.net
Vicky Coyle, Dr
- Recruiting
Edinburgh Cancer Research Centre, Western General Hospital
Edinburgh, EH4 2XR
Olga Demyanov, olga.demyanov@ed.ac.uk
Stefan Symeonides, Dr
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Jeff Evans, j.evans@beatson.gla.ac.uk
Jeff Evans, Prof
- Recruiting
Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary
Leicester, LE2 7LX
Dean Fennell, df132@leicester.ac.uk
Dean Fennell, Prof
- Recruiting
Cancer Research UK Centre, Southampton University Hospitals and University of Southampton
Southampton, SO16 6YD
Christian Ottensmeier, c.h.ottensmeier@soton.ac.uk
Christian Ottensmeier, Prof
About this study
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)
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.
Read the detailed description
Programmed cell death receptor 1 (PD-1) blockade is a well-tolerated novel cancer immunotherapy with monotherapy response rates of 20-50% in tumour types such as bladder, melanoma, renal and non-small cell lung cancer (NSCLC), along with durable benefit. However, other tumour types (such as pancreatic cancer) have been poorly responsive and it is likely that the activity of PD-1 blockade is limited in many patients by the presence of additional immunosuppressive tumour microenvironment interactions. The investigators have recently shown in preclinical studies that Focal Adhesion Kinase (FAK) inhibition can re-model multiple aspects of the tumour immune microenvironment, shifting the balance from inhibitory Tregs, TAMs, CAFs \& MDSCs, to one which supports an active CD8+ T cell adaptive immune response, suitable for synergistic anti-PD-1 therapy.
The current clinical study will explore whether FAK inhibition (defactinib/VS-6063) can be safely and tolerably combined with PD-1 blockade (pembrolizumab), with early indications of improved anticancer immunotherapy from this novel combination. The investigators will focus on three key tumour types, all cancers in clear need of improved therapies. NSCLC, aiming to augment the moderate monotherapy activity of PD-1 blockade; pancreatic cancer, aiming to release immunological activity in this otherwise resistant cancer; and, finally, mesothelioma, where emerging data suggests both agents may have monotherapy activity, including a potential additional mode of action via synthetic lethality of FAK inhibition in the ~50% of mesothelioma with NF2 mutation.
Phase I/IIa clinical study of defactinib (VS-6063, FAK inhibitor) in combination with pembrolizumab (anti-PD-1) therapy, initially in an "all-comers" dose escalation phase, and subsequently in expansion cohorts at the optimal doses in patients with: (a) pancreatic cancer; (b) NSCLC; and (c) mesothelioma. Safety, tolerability and clinical activity will be explored, as well as extensive translational work to characterise the biological effects and explore potential predictive and pharmacodynamic biomarkers.
PHASE I
Dose-escalation in an "all-comers" phase I population, with treatment-refractory advanced solid malignancies, unselected by tumour type as follows:
Cohorts 200 mg (IV) pembrolizumab every 3 weeks: plus 200 mg (oral) defactinib twice daily 200 mg (IV)pembrolizumab every 3 weeks: plus 400 mg (oral) defactinib twice daily
PHASE II
Expansions in pancreatic ductal adenocarcinoma, non-small cell lung cancer \& mesothelioma (each 15-16 evaluable patients).
Pancreatic
Pancreatic expansion for response assessment (single arm). Optional paired biopsies prior to treatment and after 14 days of treatment. 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.
- Classic "stromal" cancer, where the tumour microenvironment is believed to limit the activity of multiple agents. However broad preclinical data for various approaches to re-modelling the tumour microenvironment to permit immunotherapy.
- Minimal single-agent anti-PD-1/PD-L1 activity, explores hypothesis of conversion to sensitivity and predictive biomarkers for this.
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 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.
- Moderate single-agent anti-PD-1/PD-L1 activity explores hypothesis of amplification of sensitivity and predictive biomarkers for this.
- Paired-biopsy assessment of proof of mechanism biomarkers (FAK signalling, tumour immune microenvironment).
Mesothelioma
Mesothelioma 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 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.
- Emerging single-agent immune checkpoint, as well as potential FAK-inhibitor activity, explores hypothesis of multi-modal combination activity (microenvironment, checkpoint and synthetic lethality), as well as predictive biomarkers for this.
- Paired-biopsy assessment of proof of mechanism biomarkers (FAK signalling, tumour immune microenvironment).
- Being tested
- Defactinib, Pembrolizumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Mesothelioma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefactinibDrug
Also called VS-6063
cross reference with arm/group descriptions
PembrolizumabDrug
Also called Keytruda and MK-3475
cross reference with arm/group descriptions
| Study group | Role | What they receive |
|---|---|---|
| Dose - escalation | Experimental | 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 Receives: Drug: Defactinib; Drug: Pembrolizumab |
| Pancreatic | Experimental | 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 Receives: Drug: Defactinib; Drug: Pembrolizumab |
| NSCLC | Experimental | 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. Receives: Drug: Defactinib; Drug: Pembrolizumab |
| Mesothelioma | Experimental | 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. Receives: Drug: Defactinib; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (5)
Objective response rate (ORR), using best objective response by irRECIST
Evaluate the response rate, by irRECIST, of the combination of defactinib and pembrolizumab in patients with advanced solid malignancies.
Measured: 3 years
Duration of response (DoR)
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.
Measured: 3 years
Progression free survival (PFS)
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.
Measured: 3 years
Change in FAK Y397 phosphorylation
change in FAK Y397 phosphorylation between baseline biopsy and a repeat biopsy afer 2 weeks of therapy
Measured: 2 weeks
Change in immune cell infiltrate
change in immune cell infiltrate between baseline biopsy and a repeat biopsy after 2 weeks of therapy
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2016 (estimated)
- Study start4 Jul 2017
- Primary completionMay 2019 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-small-cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, Cancer Research UK, Merck Sharp & Dohme LLC, Verastem, Inc., University of Edinburgh, University of Southampton, University of Leicester, Queen's University, Belfast
- Responsible party
- Sponsor
- Investigators
- Stefan Symeonides, Principal investigator, Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XRJeff Evans, Principal investigator, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YNChristian Ottensmeier, Principal investigator, Cancer Research UK Centre, Southampton University Hospitals and University of Southampton, Southampton SO16 6YDDean Fennell, Principal investigator, Department of Cancer Studies, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LXVicky Coyle, Principal investigator, Belfast Health and Social Care Trust, Cancer Centre, Lisburn Road, Belfast BT9 7BL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02758587
- Sponsor's protocol ID
- GN15ON133
- Other IDs
- 2015-003928-31, 2015
- Status last verified
- Mar 2018
- First submitted
- 20 Apr 2016
- Last updated
- 19 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37598000
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02758587
- Acronym / sponsor ID
- GN15ON133
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 59 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, Cancer Research UK, Merck Sharp & Dohme LLC, Verastem, Inc., University of Edinburgh, University of Southampton, University of Leicester, Queen's University, Belfast
- Study start
- 4 Jul 2017 (actual)
- Primary completion
- May 2019 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 2 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Programmed cell death receptor 1 (PD-1) blockade is a well-tolerated novel cancer immunotherapy with monotherapy response rates of 20-50% in tumour types such as bladder, melanoma, renal and non-small cell lung cancer (NSCLC), along with durable benefit. However, other tumour types (such as pancreatic cancer) have been poorly responsive and it is likely that the activity of PD-1 blockade is limited in many patients by the presence of additional immunosuppressive tumour microenvironment interactions. The investigators have recently shown in preclinical studies that Focal Adhesion Kinase (FAK) inhibition can re-model multiple aspects of the tumour immune microenvironment, shifting the balance from inhibitory Tregs, TAMs, CAFs \& MDSCs, to one which supports an active CD8+ T cell adaptive immune response, suitable for synergistic anti-PD-1 therapy.
The current clinical study will explore whether FAK inhibition (defactinib/VS-6063) can be safely and tolerably combined with PD-1 blockade (pembrolizumab), with early indications of improved anticancer immunotherapy from this novel combination. The investigators will focus on three key tumour types, all cancers in clear need of improved therapies. NSCLC, aiming to augment the moderate monotherapy activity of PD-1 blockade; pancreatic cancer, aiming to release immunological activity in this otherwise resistant cancer; and, finally, mesothelioma, where emerging data suggests both agents may have monotherapy activity, including a potential additional mode of action via synthetic lethality of FAK inhibition in the ~50% of mesothelioma with NF2 mutation.
Phase I/IIa clinical study of defactinib (VS-6063, FAK inhibitor) in combination with pembrolizumab (anti-PD-1) therapy, initially in an "all-comers" dose escalation phase, and subsequently in expansion cohorts at the optimal doses in patients with: (a) pancreatic cancer; (b) NSCLC; and (c) mesothelioma. Safety, tolerability and clinical activity will be explored, as well as extensive translational work to characterise the biological effects and explore potential predictive and pharmacodynamic biomarkers.
PHASE I
Dose-escalation in an "all-comers" phase I population, with treatment-refractory advanced solid malignancies, unselected by tumour type as follows:
Cohorts 200 mg (IV) pembrolizumab every 3 weeks: plus 200 mg (oral) defactinib twice daily 200 mg (IV)pembrolizumab every 3 weeks: plus 400 mg (oral) defactinib twice daily
PHASE II
Expansions in pancreatic ductal adenocarcinoma, non-small cell lung cancer \& mesothelioma (each 15-16 evaluable patients).
Pancreatic
Pancreatic expansion for response assessment (single arm). Optional paired biopsies prior to treatment and after 14 days of treatment. 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.
- Classic "stromal" cancer, where the tumour microenvironment is believed to limit the activity of multiple agents. However broad preclinical data for various approaches to re-modelling the tumour microenvironment to permit immunotherapy.
- Minimal single-agent anti-PD-1/PD-L1 activity, explores hypothesis of conversion to sensitivity and predictive biomarkers for this.
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 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.
- Moderate single-agent anti-PD-1/PD-L1 activity explores hypothesis of amplification of sensitivity and predictive biomarkers for this.
- Paired-biopsy assessment of proof of mechanism biomarkers (FAK signalling, tumour immune microenvironment).
Mesothelioma
Mesothelioma 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 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.
- Emerging single-agent immune checkpoint, as well as potential FAK-inhibitor activity, explores hypothesis of multi-modal combination activity (microenvironment, checkpoint and synthetic lethality), as well as predictive biomarkers for this.
- Paired-biopsy assessment of proof of mechanism biomarkers (FAK signalling, tumour immune microenvironment).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose - escalation | Experimental | Drug: Defactinib, Drug: PembrolizumabDoes-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 | Experimental | Drug: Defactinib, Drug: PembrolizumabPancreatic 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 | Experimental | Drug: Defactinib, Drug: PembrolizumabNSCLC 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 | Experimental | Drug: Defactinib, Drug: PembrolizumabMesothelioma 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DefactinibAlso: VS-6063cross reference with arm/group descriptions | Drug | Dose - escalation, Mesothelioma, NSCLC, Pancreatic |
| PembrolizumabAlso: Keytruda and MK-3475cross reference with arm/group descriptions | Drug | Dose - escalation, Mesothelioma, NSCLC, Pancreatic |
Primary outcome
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.
5 secondary outcomes
Objective response rate (ORR), using best objective response by irRECIST
Time frame: 3 years
Duration of response (DoR)
Time frame: 3 years
Progression free survival (PFS)
Time frame: 3 years
Change in FAK Y397 phosphorylation
Time frame: 2 weeks
Change in immune cell infiltrate
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2018.
- Derived from this study: PubMed 37598000Fard 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Symeonides principal investigator
Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR
Jeff Evans principal investigator
Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN
Christian Ottensmeier principal investigator
Cancer Research UK Centre, Southampton University Hospitals and University of Southampton, Southampton SO16 6YD
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Defactinib and Pembrolizumab in people with Carcinoma, Non-small-cell Lung and Mesothelioma, run by NHS Greater Glasgow and Clyde at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dawn Currie (00 44 141 301 7194, dawn.currie@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AEs) using CTCAE v4.03 (to determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD)) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02758587, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2018.