Clinical Study of BDB018: Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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A Phase 1 Open-label Dose Escalation Trial of BDB018 in Monotherapy and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

Detailed Description
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This clinical trial is a study of an experimental drug called BDB018. BDB018 is a next-generation Toll-like receptor (TLR) 7/8 agonist that activates the immune system. The primary objectives of this study are to evaluate the safety and tolerability of BDB018 in monotherapy and in combination with pembrolizumab (Keytruda) in subjects with unresectable or metastatic solid tumors that have relapsed or are refractory to standard treatment or for which there is no approved therapy. This is a multi-center, open-label, dose escalation/dose expansion Phase 1 study of BDB018 in monotherapy and in combination with pembrolizumab. The study will be conducted in two separate but independent parts: a dose escalation part with BDB018 in monotherapy and in combination with pembrolizumab and a dose expansion part of BDB018 in combination with pembrolizumab.

Official Title
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Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Conditions
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Tumor, Solid

Intervention / Treatment
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* Drug: BDB018
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically or cytologically confirmed advanced or metastatic solid tumors that have disease progression after treatment with all available therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Note: there is no limit to the number of prior treatment regimens Evidence of progressive disease (PD) within 3 months of signing the informed consent form. Have measurable disease Exclusion Criteria: Has disease that is suitable for local therapy administered with curative intent. Prior exposure to TLR7 agonists, TLR8 agonists, TLR 7/8 dual agonists, and TLR9 agonists. Other protocol defined inclusion/exclusion criteria could apply

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: BDB018 in Monotherapy<br>A single subject will be enrolled at each dose level in the single agent arm. Then dosage escalation will follow a traditional 3+3 dose escalation design. Each successive group of patients will be enrolled at an incrementally higher dosage until the Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D) of single agent BDB018 is reached. | Drug: BDB018<br>* BDB018 is an immunotherapy agent.<br>|
| Experimental: BDB018 in Combination with Pembrolizumab<br>In the combination arm of the study, a standard 3+3 dose escalation design will be utilized for all dose levels. When the MTD or RP2D of single agent BDB018 is reached, the first dose level cohort of the combination arm will begin. Once the MTD or RP2D in combination has been determined, approximately twenty additional subjects will be enrolled in the expansion phase of the study. | Drug: BDB018<br>* BDB018 is an immunotherapy agent.<br>Drug: Pembrolizumab<br>* Pembrolizumab is a potent humanized monoclonal antibody with high specificity of binding to the PD 1 receptor. Pembrolizumab has an acceptable preclinical safety profile and is approved as an IV therapy for a variety of advanced malignancies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability: incidence of adverse events and any dose limiting toxicity | Safety and tolerability of BDB018 in monotherapy and in combination with pembrolizumab as measured by the incidence of adverse events and any dose limiting toxicity | Up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Maximum Tolerated Dose | Determination of the maximum tolerated dose by assessing the frequency of BDB018 related and BDB018 and pembrolizumab-related adverse events using CTCAE version 5.0 to categorize adverse event severity | From first dose to 21 days after first dose for each patient (cycle 1) | 
| Radiographic Determination of Tumor Response after BDB018 Dosing | Radiographic determination of tumor response in subjects dosed with BDB018 and BDB018 and pembrolizumab combination therapy using irRECIST | Every 63 days (3 cycles) up to 30 months after the first dose for each patient (each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TLR, Immuno-oncology, TLR 7/8 Agonist