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.

Phase 1

• Conditions: Advanced, incurable cancer with no remaining standard-of-care treatment options that are suitable. Or where pembrolizumab is a licensed treatment option at that line of therapy. In Phase I, this may be any solid cancer. In Phase II, this will be pancreatic cancer, non-small cell lung cancer (NSCLC) or mesothelioma.; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10033633Term: Pancreatic neoplasms malignant (excl islet cell and carcinoid)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10029664Term: Non-small cell neoplasms malignant of the respiratory tract cell type specifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10027414Term: Mesotheliomas malignant and unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003928-31-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-07
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

All parts of study
1.Informed, written consent
2.Male or female, aged 18 years or older at the time consent is given
3.ECOG performance status 0 or 1, with no deterioration over the previous 2 weeks
4.Life expectancy of at least 3 months
5.Measurable disease according to irRECIST criteria, with at least one measurable lesion that has objectively progressed since (or on) any previous therapy
6.Adequate bone marrow, liver and renal function on blood investigations within 7 days prior to treatment initiation:
a.Creatinine = 1.5 x ULN OR GFR = 60 mls/min for patients with creatinine levels > 1.5 x ULN. (using the standard methodology at the investigating centre - i.e Cockcroft-Gault, Wright, MDRD or CKD-EPI formulae, EDTA clearance or 24 urine collection)
b.Total bilirubin = 1.5 x ULN
c.Alanine transaminase (ALT) and/or aspartate transaminase (AST) = 2.5 x ULN (if both measured, both must meet criteria)
d.White blood cell count = 3.0 x 109/L
e.Absolute Neutrophil Count (ANC) = 1.5 x 109/L
f.Platelets = 100 x 109/L
g.Haemoglobin = 90 g/L
h.International Normalized Ratio (INR) or Prothrombin Time (PT) = 1.5 x ULN, UNLESS patient is receiving anticoagulation therapy, in which case INR or PT must be within the intended therapeutic range.
7.Patients must have been offered all appropriate standard-of-care treatments (or all those indicated before anti-PD-1/PD-L1 therapy, if licensed)
8.Patients must agree to use adequate contraceptive measures for the course of the study through 120 days after the last dose of study medication
9.Women of child-bearing potential must have a negative pregnancy test within 72 hours prior to start of dosing
10.Consent to supply any available archival tissue

Dose escalation (Phase I)
11.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)
12.Pathological diagnosis of pancreatic ductal adenocarcinoma, with confirmation that a tissue sample (core biopsy or resected specimen) is available

NSCLC expansion (Phase IIa)
13.Pathological diagnosis of non-small cell lung cancer (NSCLC)
14.Lesion suitable for repeat biopsy
15.Baseline biopsy containing tumour material during eligibility
16.Consent for paired biopsies on study

Mesothelioma expansion (Phase IIa)
17.Pathological diagnosis of mesothelioma
18.Lesion suitable for repeat biopsy
19.Baseline biopsy containing tumour material during eligibility
20.Consent for paired biopsies on study

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

All parts of study
1.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)
2.Any central nervous system metastases unless treated and asymptomatic, as well as stable on imaging and not requiring steroids in the preceding 4 weeks
3.Any interventional studies, systemic cancer therapies or monoclonal antibodies in the preceding 4 weeks (6 weeks for mitomycin C and nitrosureas)
4.Any live vaccines in the preceding 4 weeks
5.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.
6.Diagnosis of immunodeficiency
7.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
8.Known interstitial lung disease or active, non-infectious pneumonitis
9.Known history of Tuberculosis (TB), Human Immunodeficiency Virus (HIV) or active Hepatitis B or C
10.Other severe or uncontrolled systemic diseases (e.g. uncontrolled hypertension, recent myocardial infarction, organ failure or active infection)
11.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
12.Pregnancy or lactation
13.Limited ability to swallow or absorb oral medications
14.Hypersensitivity to defactinib (VS-6063), pembrolizumab or excipients (including L-histidine, L-histidine hydrochloride monohydrate, sucrose or polysorbate 80)
15.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 the best interest of the subject to participate, in the opinion of the treating investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified