Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab

Study Overview
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Brief Summary
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This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab. The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.

Official Title
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Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: FLX475
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies Dose Escalation: non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma Dose Expansion: nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts) Tumor available for biopsy Exclusion Criteria: History of allergy or severe hypersensitivity to biologic agents History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant Active graft-versus-host disease

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1a: Monotherapy Dose Escalation<br>Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy. | Drug: FLX475<br>* tablet<br>|
| Experimental: Part 1b: Combination Dose Escalation<br>Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab. | Drug: FLX475<br>* tablet<br>Drug: Pembrolizumab<br>* IV infusion<br>* Other names: Keytruda;|
| Experimental: Part 2a: Monotherapy Expansion Cohorts<br>Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2. | Drug: FLX475<br>* tablet<br>|
| Experimental: Part 2b: Combination Expansion Cohorts<br>Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2. | Drug: FLX475<br>* tablet<br>Drug: Pembrolizumab<br>* IV infusion<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of FLX475 as a single agent and in combination with pembrolizumab measured by the incidence of adverse events, including dose-limiting toxicities and maximum tolerated dose |  | Approximately 18 weeks | 
| Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab |  | Through study completion (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Breast Cancer, Urothelial Carcinoma, Nasopharyngeal Carcinoma, Cervical Cancer, Lymphoma