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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Solid Tumor
• Intervention / Treatment: Drug: TTX-030; Drug: Pembrolizumab; Drug: Gemcitabine; Drug: nab paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Center Oncology Hematology West P.C.
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center and Research Institute
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Intitute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Abreviated Inclusion Criteria

1. 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.
2. Age 18 years or older, is willing and able to provide informed consent
3. Evidence of measurable disease
4. Life expectancy > 12 weeks and Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Abbreviated Exclusion Criteria

1. History of allergy or hypersensitivity to study treatment components. Patients with a history of severe hypersensitivity reaction to any monoclonal antibody.
2. Use of investigational agent within 28 days prior to the first dose of study treatment and throughout the study
3. Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy
4. History of severe autoimmune disease
5. Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Trishula Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): September 29, 2023

Study Registration Dates

• First Submitted: March 16, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Gemcitabine; Docetaxel; Cancer; Lung Cancer; Immunotherapy; Pancreatic Cancer; Checkpoint Inhibitor; Pembrolizumab; PD-1; Advanced Solid Tumors; Metastatic Solid Tumors; Combination Therapy; Bladder Cancer; Immuno-oncology; Nab-paclitaxel; Monotherapy; CD39; Adenosine Pathway; Relapsed/Refractory Lymphoma; Prostrate Cancer
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Pembrolizumab; Gemcitabine
• Other Study ID Numbers: TTX-030-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No