TTX-030 in Combination With Immunotherapy and/or Chemotherapy in Subjects 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 in combination therapy, 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, pharmacodynamics and anti-tumor activity of TTX-030 in combination with immunotherapy and/or standard chemotherapies.

Official Title
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Phase 1/1b Study to Evaluate the Safety and Activity of TTX-030 (Anti-CD39) in Combination With Pembrolizumab or Budigalimab and/or Chemotherapy in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Combination Product: TTX-030, budigalimab and mFOLFOX6
* Combination Product: TTX-030, budigalimab and docetaxel
* Combination Product: TTX-030 and mFOLFOX6
* Combination Product: TTX-030 and budigalimab
* Combination Product: TTX-030, budigalimab, nab-paclitaxel and gemcitabine
* Combination Product: TTX-030 and pembrolizumab
* Combination Product: TTX-030, nab-paclitaxel and gemcitabine
* Combination Product: Budigalimab and mFOLFOX6


Participation Criteria
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Eligibility Criteria
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Abbreviated Inclusion Criteria: Age 18 years or older, is willing and able to provide informed consent Histologically confirmed diagnosis of unresectable or metastatic solid tumor malignancy in selected tumor types Life expectancy > 12 weeks 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
Maximum Age: 110 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: Combo 1<br>TTX-030 plus budigalimab plus mFOLFOX6 | Combination Product: TTX-030, budigalimab and mFOLFOX6<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 2<br>TTX-030 plus budigalimab plus docetaxel | Combination Product: TTX-030, budigalimab and docetaxel<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 3<br>TTX-030 plus mFOLFOX6 | Combination Product: TTX-030 and mFOLFOX6<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 4<br>TTX-030 plus pembrolizumab | Combination Product: TTX-030 and pembrolizumab<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 5<br>TTX-030 plus budigalimab (selected tumors evaluated in expansion) | Combination Product: TTX-030 and budigalimab<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 6<br>TTX-030 plus budigalimab plus nab-paclitaxel + gemcitabine | Combination Product: TTX-030, budigalimab, nab-paclitaxel and gemcitabine<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 7<br>TTX-030 plus nab-paclitaxel + gemcitabine | Combination Product: TTX-030, nab-paclitaxel and gemcitabine<br>* Dose and schedule per protocol<br>|
| Experimental: Combo 8<br>Budigalimab plus mFOLFOX6 | Combination Product: Budigalimab and mFOLFOX6<br>* Dose and schedule per protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of study subjects experiencing adverse events (AEs), dose-limiting toxicities, and serious adverse events (SAEs). Safety profile will be assessed through laboratory evaluations, vital signs, and physical examinations. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects with CR or PR | Through study completion, an average of 1 year | 
| Duration of response (DoR) | DoR will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first. | Through study completion, an average of 1 year | 
| Disease control rate (DCR) | DCR is defined as the proportion of subjects with CR, PR, or SD | Through study completion, an average of 1 year | 
| Progression-free survival (PFS) | PFS is measured from documentation of progression or death from any cause, whichever occurs first | Through study completion, an average of 1 year | 
| Pharmacokinetics (PK) | Serum concentrations of TTX-030 will be tabulated | Cycles 1-4 (each cycle is 21-28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric (gastroesophageal cancer), Advanced Solid Tumor, Colorectal cancer, Cancer, Metastatic Solid Tumor, Combination Therapy, CD39, Adenosine Pathway, Immunotherapy Immuno-oncology, PD-1 Checkpoint Inhibitor, Docetaxel, Budigalimab, ABBV-181, TTX-030, Non-small cell lung cancer, Urothelial cell cancer, Pancreatic cancer, Pembrolizumab, Keytruda, Bladder cancer, Gemcitabine, Nab-paclitaxel