TTX-030 Single Agent and in Combination With Immunotherapy or Chemotherapy for Patients With Advanced Cancers

Study Overview
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Brief Summary
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This is a phase 1/1b study of TTX-030, an antibody that inhibits CD39 enzymatic activity, leading to accumulation of pro-inflammatory adenosine triphosphate (ATP) and reduction of immunosuppressive adenosine, which may change the tumor microenvironment and promote anti-tumor immune response. This trial will study the safety, tolerability, pharmacokinetics, and anti-tumor activity of TTX-030 as a single agent and in combination with an approved anti-PD-1 immunotherapy and standard chemotherapies.

Official Title
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Phase 1/1b Study of the Safety of TTX-030 as a Single Agent and in Combination With Pembrolizumab or Chemotherapy in Patients With Lymphoma or Solid Tumor Malignancies

Conditions
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Solid Tumor, Lymphoma

Intervention / Treatment
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* Drug: TTX-030
* Drug: Pembrolizumab
* Drug: Gemcitabine
* Drug: nab paclitaxel


Participation Criteria
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Eligibility Criteria
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Abreviated Inclusion Criteria Advanced solid tumor malignancy or relapsed/refractory lymphoma, or eligible to receive single-agent pembrolizumab as standard of care, or eligible to receive single-agent docetaxel as standard of care, or advanced pancreatic adenocarcinoma and eligible to receive gemcitabine plus nab-paclitaxel as standard of care. Age 18 years or older, is willing and able to provide informed consent Evidence of measurable disease Life expectancy > 12 weeks and Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Abbreviated Exclusion Criteria History of allergy or hypersensitivity to study treatment components. Patients with a history of severe hypersensitivity reaction to any monoclonal antibody. Use of investigational agent within 28 days prior to the first dose of study treatment and throughout the study Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy History of severe autoimmune disease Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment

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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1, Single Agent<br>TTX-030 | Drug: TTX-030<br>* Variable dose and schedule<br>|
| Experimental: Arm 2, Anti-PD-1 Combination<br>TTX-030 plus pembrolizumab | Drug: TTX-030<br>* Variable dose and schedule<br>Drug: Pembrolizumab<br>* Dose and schedule per standard of care<br>|
| Experimental: Arm 4, Chemotherapy Combination<br>TTX-030 plus gemcitabine plus nab-paclitaxel | Drug: TTX-030<br>* Variable dose and schedule<br>Drug: Gemcitabine<br>* Dose and schedule per standard of care<br>Drug: nab paclitaxel<br>* Dose and schedule per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Phase 2 Dose (RP2D) | Assess the safety profile, dose limiting toxicity (DLT), maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TTX-030 when administered intravenously (IV) as a single agent and in combination with agents in specified regimens to subjects with advanced solid tumor malignancies or lymphoma | 1 cycle (each cycle is 21-28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity | Anti-tumor activity in subjects treated with TTX-030 as single agent or in combination with specified regimens | Through study completion, an average of 1 year | 
| Maximum Plasma Concentration (Cmax) | Pharmacokinetics (PK) of TTX-030 | Cycles 1-3 (each cycle is 21-28 days) | 
| CD39 Expression | Pharmacodynamic (PD) biomarkers relating to mechanism of action and immune responses | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD39, Cancer, Metastatic Solid Tumors, Advanced Solid Tumors, Relapsed/Refractory Lymphoma, Prostrate Cancer, Pancreatic Cancer, Monotherapy, Combination Therapy, Adenosine Pathway, Immunotherapy, Immuno-oncology, PD-1, Checkpoint Inhibitor, Nab-paclitaxel, Gemcitabine, Pembrolizumab, Docetaxel, Bladder Cancer, Lung Cancer