TTX-030 in Combination With Immunotherapy and/or Chemotherapy in Subjects With Advanced Cancers

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: 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 pembrolizumab; Combination product: TTX-030 and budigalimab; Combination product: TTX-030, budigalimab, nab-paclitaxel and gemcitabine; Combination product: TTX-030, nab-paclitaxel and gemcitabine; Combination product: Budigalimab and mFOLFOX6

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan
    • Seogu, Busan, Korea, Republic of, 49201
      • National Cancer Center
  • Goyang-si, Gyeonggi-do
    • Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
  • Kyunggi-do
    • Seongnam-si Bundan-gu, Kyunggi-do, Korea, Republic of, 13620
      • Seoul National University
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 06351
      • Samsung Medical Center
    • Seodaemun-gu, Seoul, Korea, Republic of, 03722
      • Severance Hospital Yonsei University
    • Songpa-gu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center Clinical Trials Office
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90007
      • University of Southern California
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology
    • Orange, California, United States, 92868
      • Chao Family Comprehensive CC, UCI
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center PL
    • Orlando, Florida, United States, 32835
      • Orlando Health UF Health Cancer Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health - John B. Amos Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Center Oncology Hematology West P.C.
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • University Hospitals Cleveland Medical Center
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma-Health Cancer Institute
  • 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
      • Hunstman Cancer Intitute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Abbreviated Inclusion Criteria:

1. Age 18 years or older, is willing and able to provide informed consent
2. Histologically confirmed diagnosis of unresectable or metastatic solid tumor malignancy in selected tumor types
3. Life expectancy > 12 weeks
4. 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combo 1; TTX-030 plus budigalimab plus mFOLFOX6	Combination product: TTX-030, budigalimab and mFOLFOX6; Dose and schedule per protocol
Experimental: Combo 2; TTX-030 plus budigalimab plus docetaxel	Combination product: TTX-030, budigalimab and docetaxel; Dose and schedule per protocol
Experimental: Combo 3; TTX-030 plus mFOLFOX6	Combination product: TTX-030 and mFOLFOX6; Dose and schedule per protocol
Experimental: Combo 4; TTX-030 plus pembrolizumab	Combination product: TTX-030 and pembrolizumab; Dose and schedule per protocol
Experimental: Combo 5; TTX-030 plus budigalimab (selected tumors evaluated in expansion)	Combination product: TTX-030 and budigalimab; Dose and schedule per protocol
Experimental: Combo 6; TTX-030 plus budigalimab plus nab-paclitaxel + gemcitabine	Combination product: TTX-030, budigalimab, nab-paclitaxel and gemcitabine; Dose and schedule per protocol
Experimental: Combo 7; TTX-030 plus nab-paclitaxel + gemcitabine	Combination product: TTX-030, nab-paclitaxel and gemcitabine; Dose and schedule per protocol
Experimental: Combo 8; Budigalimab plus mFOLFOX6	Combination product: Budigalimab and mFOLFOX6; Dose and schedule per protocol

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Trishula Therapeutics, Inc.
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2020
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): March 27, 2024

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Docetaxel; Cancer; Colorectal cancer; Bladder cancer; Non-small cell lung cancer; Pembrolizumab; Keytruda; Pancreatic cancer; Combination Therapy; Advanced Solid Tumor; Metastatic Solid Tumor; Nab-paclitaxel; ABBV-181; Budigalimab; Gastric (gastroesophageal cancer); CD39; Adenosine Pathway; Immunotherapy Immuno-oncology; PD-1 Checkpoint Inhibitor; TTX-030; Urothelial cell cancer
• Additional Relevant MeSH Terms: Neoplasms; 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; Docetaxel; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: TTX-030-002

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