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

Sponsor

Trishula Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03884556

Collaborator

(none)

Enrollment

Locations

Arms

43.7

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Lymphoma	Drug: TTX-030 Drug: Pembrolizumab Drug: Gemcitabine Drug: nab paclitaxel	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 10, 2019

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Recommended Phase 2 Dose (RP2D) [1 cycle (each cycle is 21-28 days)]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Irvine Cancer Center	Orange	California	United States	92868
2	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	University of California, San Francisco	San Francisco	California	United States	94143
4	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
5	Norton Cancer Institute	Louisville	Kentucky	United States	40202
6	Nebraska Cancer Center Oncology Hematology West P.C.	Omaha	Nebraska	United States	68130
7	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
8	Montefiore Medical Center	Bronx	New York	United States	10461
9	Columbia University Irving Medical Center	New York	New York	United States	10032
10	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
11	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44122
12	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
13	West Cancer Center and Research Institute	Germantown	Tennessee	United States	38138
14	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
15	NEXT Oncology	San Antonio	Texas	United States	78229
16	Huntsman Cancer Intitute	Salt Lake City	Utah	United States	84112