Efficacy and Safety Evaluation of TTX-030 and Chemotherapy With or Without Budigalimab in Untreated Metastatic Pancreatic Adenocarcinoma
- Trial ID
- 2023-508356-19-00
- Protocol
- TTX-030-003
- Sponsor
- Trishula Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the benefit of adding **TTX-030** with or without **budigalimab** to the standard chemotherapy regimen of **nab-paclitaxel** and **gemcitabine** in patients with metastatic pancreatic adenocarcinoma. This evaluation is crucial as it may enhance treatment efficacy for a population that has not previously received treatment for this condition, potentially improving clinical outcomes.
Secondary objectives include:
- Evaluating the benefit of the addition of TTX-030 with or without budigalimab to nab-paclitaxel and gemcitabine in both the overall and target populations.
- Assessing the safety profile associated with the addition of TTX-030 with or without budigalimab in combination with nab-paclitaxel and gemcitabine.
Participants
The clinical trial involves a total of **123 participants** diagnosed with **metastatic pancreatic adenocarcinoma**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific inclusion criteria, such as having a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma (PDAC) and being appropriate for treatment with nab-paclitaxel and gemcitabine chemotherapy. The trial excludes individuals with prior systemic treatment for metastatic disease or those who have received therapeutics targeting anti-tumor immunity. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population is characterized by a general health status that allows for compliance with study protocols, including the ability to provide informed consent and adhere to contraception requirements if applicable. Lifestyle considerations such as diet and physical activity are not specified, but participants must meet baseline laboratory test requirements and have no contraindications for biopsy procedures if tumor tissue is unavailable. The trial includes a vulnerable population, ensuring ethical considerations are addressed in the study design.
Plans and Procedures
The clinical trial is designed as an open-label, multicenter, three-arm, randomized Phase 2 study. It aims to assess the efficacy and safety of **TTX-030** and chemotherapy with or without **Budigalimab**, compared to chemotherapy alone, in patients with metastatic pancreatic adenocarcinoma who have not received prior treatment for their metastatic condition. The trial will involve a total duration of approximately 24 months for each participant, with the overall study expected to conclude by February 2027. Participants will be randomly assigned to one of the three treatment arms, ensuring a controlled comparison of the therapeutic interventions.
The study will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as a confirmed diagnosis of metastatic pancreatic adenocarcinoma and appropriate baseline laboratory tests. Following successful screening, participants will undergo a series of study visits, including regular follow-up visits to monitor treatment response and safety. These visits will involve assessments of progression-free survival, objective response rate, duration of response, and overall survival, alongside evaluations of treatment-emergent adverse events. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted to gather comprehensive data on the trial's primary and secondary endpoints.
Participant involvement is expected to last for the entire 24-month treatment period unless conditions arise that necessitate early termination. Such conditions may include significant adverse events, disease progression, or withdrawal of consent. The trial's methodology ensures rigorous monitoring and data collection to evaluate the potential benefits of adding TTX-030 and Budigalimab to the standard chemotherapy regimen of nab-paclitaxel and gemcitabine. The study's design and procedures are structured to provide robust evidence on the therapeutic efficacy and safety of the investigational treatments in the target population.
Treatment
The clinical trial involves the administration of **Budigalimab**, an experimental medication formulated as a **solution for injection/infusion**. Budigalimab is administered via **intravenous infusion**. The maximum daily dose is 250 mg, with a total maximum dose of 12,500 mg over a treatment period of 24 weeks. The active substance, Budigalimab, is a protein of non-specific origin, developed by AbbVie Deutschland GmbH & Co. KG. Participant compliance with the dosing schedule will be monitored throughout the trial.
Another experimental medication used in the trial is **TTX-030**, provided as a **solution for infusion**. This medication is also administered through **intravenous infusion**. The dosing regimen allows for a maximum daily dose of 40 mg/kg, with a total maximum dose of 1,020 mg/kg over a 24-week period. TTX-030 is a protein-based substance developed by Trishula Therapeutics Inc. Compliance with the administration schedule will be closely monitored to ensure adherence.
The trial also includes the use of **Paclitaxel**, a non-experimental treatment, classified under antineoplastic agents. Paclitaxel is administered as an **intravenous infusion** with a pharmaceutical form denoted as PHF00230MIG. The maximum daily dose is 250 mg/m², with a total maximum dose of 3,125 mg/m² over the course of 24 weeks. Paclitaxel is a chemical substance, and its administration will be monitored to ensure proper dosing and participant compliance.
Additionally, **Gemcitabine Hydrochloride** is utilized in the study, categorized as a pyrimidine analogue. It is administered via **intravenous infusion**, also in the form of PHF00230MIG. The dosing schedule permits a maximum daily dose of 1,000 mg/m², with a total maximum dose of 25,000 mg/m² over a 24-week period. As a chemical substance, Gemcitabine Hydrochloride's administration will be monitored to ensure adherence to the prescribed dosing regimen.
Efficacy
The efficacy of the clinical trial will be assessed using several key endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, which measures the length of time during and after treatment that a patient lives with the disease without it getting worse. Secondary endpoints include Objective Response Rate (ORR), Duration of Response (DoR), and Overall Survival (OS). These endpoints will provide a comprehensive evaluation of the treatment's impact on the disease.
The trial will involve the administration of TTX-030 and chemotherapy with or without Budigalimab, compared to chemotherapy alone, in patients with metastatic pancreatic adenocarcinoma. The efficacy parameters will be collected and analyzed at various timepoints throughout the study, although specific timepoints are not detailed in the provided data. The study will utilize standard clinical trial methodologies to ensure the accuracy and reliability of the efficacy assessments.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Male or female subjects ≥18 years of age at the time of screening.
- Histologically or cytologically confirmed diagnosis of metastatic PDAC.
- No prior systemic treatment for metastatic disease. Prior neoadjuvant or adjuvant systemic chemotherapy is permitted in the absence of disease progression within 6 months following last dose of chemotherapy.
- No prior treatment with therapeutics specifically targeted to enhancing or de-repressing anti-tumor immunity including but not limited to checkpoint inhibitors or agents targeting the adenosine pathway (CD39, CD73 or adenosine receptor inhibitors).
- Evidence of measurable disease as assessed by the investigator per RECIST 1.1.
- Appropriate for treatment with nab-paclitaxel and gemcitabine chemotherapy.
- Availability of tumor tissue (obtained by biopsy during screening, or archival if collected within 90 days prior to the first dose of study drug and in the absence of intervening therapy). Subjects with contraindications for a biopsy procedure and without acceptable archival tissue samples are not eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Subject must weigh ≥35 kg.
- Resolution of adverse events from any prior chemotherapy, immunotherapy, or prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy).
- Women of childbearing potential and all men must agree to use 2 highly effective methods of contraception through 6 months (180 days) after the last administration of any study treatment. Note: Highly effective contraception methods include total abstinence; female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy); male sterilization (at least 6 months prior to Screening); intrauterine device or intrauterine hormone-releasing system; oral, injected, or implanted hormonal contraception with only progestogen at least 30 days before first dose; AND barrier methods of contraception; oral, injectable, transdermal, or intravaginal combined hormonal contraception with estrogen and progestogen at least 30 days before first dose (Prescribing information should be followed if different from the above).
- Subjects with history of congestive heart failure must have cardiac echocardiogram (ECHO) or multigated acquisition (MUGA) scan indicating left ventricular ejection fraction ≥45% within 28 days prior to the first dose of study treatment.
- Required baseline laboratory tests: a. Hematology: absolute neutrophil count (ANC) ≥1.2 k/μL, platelets ≥100 k/μL, hemoglobin (Hgb) ≥9 g/dL b. Coagulation: prothrombin time (PT) and International Normalized Ratio (INR) ≤1.2 x upper limit of normal (ULN), except for subjects receiving anticoagulation; subjects must be on a stable dose of warfarin for 6 weeks prior to enrollment. c. Kidney: Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) ≥40 mL/min calculated by Cockcroft-Gault or CKD-EPI (Appendix 6) d. Liver: AST and ALT ≤2.5 x ULN (or ≤5 x ULN with hepatic metastases); total bilirubin ≤2 x ULN (or ≤3 x ULN with Gilbert’s syndrome); serum albumin ≥3.0 g/dL
Exclusion Criteria
- History of clinically significant allergy or hypersensitivity to planned study treatment components or to any monoclonal antibody (defined as any Grade 3 reaction lasting ≥48 hours despite optimal therapy)
- History of SJS, Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)
- History of autoimmune disease including but not limited to rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, non-infectious pneumonitis, interstitial lung disease (ILD), requiring systemic treatment that required systemic steroids or immunosuppressive agents within the last 2 years. Subjects with findings consistent with active autoimmune disease on screening evaluation (computed tomography [CT] showing pneumonitis or ILD, physical examination findings) are not eligible. NOTE: History of vitiligo, autoimmune thyroiditis, or mild psoriasis are allowed.
- Any active disease requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to Day 1 of treatment. (NOTE: Inhaled, intranasal, intra-articular and topical [including ocular] steroids are allowed. Adrenal replacement [i.e., physiologic replacement] doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease).
- History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis
- Use of investigational agent within 14 days prior to the first dose of study drug
- Evidence of active central nervous system (CNS) metastatic disease or carcinomatous meningitis
- Known history of human immunodeficiency virus (HIV) or other chronic immunodeficiency
- Women who are pregnant or breastfeeding
- Subject has received live vaccine within 28 days prior to the first dose of study drug
- The subject has had major surgery per the Investigator within 28 days prior to the first dose of study drug, and the surgical wound is not adequately healed. A diagnostic or research biopsy does not exclude subjects from enrollment. Placement of a vascular access device such as a Port-A-Cath is not considered major surgery.
- Has uncontrolled intercurrent illness including, but not limited to: a. Uncontrolled diabetes b. New York Heart Association (NYHA) Class 3 or 4 congestive heart failure c. Unstable angina, arrhythmia, or myocardial infarction within 6 months prior to screening d. Poorly controlled hypertension, defined as a blood pressure consistently above 160/90 mmHg despite optimal medical management e. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed f. Active or chronic viral hepatitis B or C infection g. Uncontrolled thyroid disease h. Active infection requiring systemic therapy; subjects receiving ongoing systemic antibiotic, antiviral or antifungal therapy for maintenance should be discussed with the medical monitor prior to screening and enrollment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 30 Jun 2024 | 7 |
 France | Not Recruiting | 30 Jun 2024 | 7 |
 Italy | Not Recruiting | 30 Jun 2024 | 16 |
 Spain | Not Recruiting | 30 Jun 2024 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Budigalimab | Test | SOLUTION FOR INJECTION/INFUSION | INTRAVENIOUS INFUSION | 250 | 24 | PRD10277708 |
PACLITAXEL | Other | PHF00230MIG | INTRAVENOUS INFUSION | 250 | 24 | SCP129816 |
TTX-030 | Test | SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 40 | 24 | PRD10991248 |
GEMCITABINE | Other | PHF00230MIG | INTRAVENIOUS INFUSION | 1000 | 24 | SCP1128788 |