Phase I Study of WX-037 Alone and in Combination With WX-554 in Solid Tumours

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of escalating doses of the novel PI3K inhibitor WX-037 and to explore its effectiveness in combination with WX-554 which targets mitogen activated protein kinase (MEK1 and MEK2). Preclinical evidence indicates that these two novel compounds could provide targeted inhibition of both pathways to block tumour growth.

Official Title
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A Phase I Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the PI3K Inhibitor WX-037, Given as a Single Agent and in Combination With the MEK Inhibitor WX-554, in Patients With Solid Tumors

Conditions
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Advanced Solid Tumours

Intervention / Treatment
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* Drug: WX-037
* Drug: WX-554


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced, metastatic and/or progressive solid tumors for whom there is no effective standard therapy available (for part 2 in addition patients for whom their PI3K pathway is deregulated) Evaluable or measurable disease Has normal organ function; is no greater than 2 on the ECOG performance scale Negative hCG test in women of childbearing potential Exclusion Criteria: History of diabetes requiring daily medication or history of grade 3 or more fasting hyperglycemia Patients with major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study Clinical significant, unresolved toxicity from previous anti-cancer therapy Patients who previously received a MEK inhibitor (for combination part only) Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis (combination part only) Known HIV positivity or active hepatitis B or C infection History of clinically significant cardiac condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WX-037<br>PI3K inhibitor | Drug: WX-037<br> <br> |
| Experimental: WX-037 in combination with WX-554<br>PI3K inhibitor in combination with MEK inhibitor | Drug: WX-037<br> <br> Drug: WX-554<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose limiting toxicities |  | during cycle 1 (21days) of treatment with WX-037 | 
| Incidence of Dose Limiting toxicities |  | during cycle 1 (21 days) of treatment with WX-037 and WX-554 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse Events and serious adverse events |  | from cycle 1 day 1 until treatment discontinuation, an estimated average of 18 weeks | 
| Assessment of PK variables, peak plasma concentration (Cmax), area under the curve (AUC) |  | two PK profiles in cycle 1 | 
| Determination of PD markers; changes from baseline in biomarkers of pathway inhibition |  | predose until treatment discontinuation, an estimated average of 18 weeks |