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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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03884556
Enrollment
56
Registered
2019-03-21
Start date
2019-04-10
Completion date
2023-09-29
Last updated
2025-07-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma, Solid Tumor

Keywords

Cancer, Metastatic Solid Tumors, Advanced Solid Tumors, Relapsed/Refractory Lymphoma, Prostrate Cancer, Pancreatic Cancer, Monotherapy, Combination Therapy, CD39, Adenosine Pathway, Immunotherapy, Immuno-oncology, PD-1, Checkpoint Inhibitor, Nab-paclitaxel, Gemcitabine, Pembrolizumab, Docetaxel, Bladder Cancer, Lung Cancer

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.

Interventions

DRUGTTX-030

Variable dose and schedule

DRUGPembrolizumab

Dose and schedule per standard of care

DRUGGemcitabine

Dose and schedule per standard of care

DRUGnab paclitaxel

Dose and schedule per standard of care

Sponsors

Trishula Therapeutics, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)1 cycle (each cycle is 21-28 days)A DLT was defined as any clinically significant AE that occurred during Treatment Cycle 1 that the Investigator or Sponsor considered as possibly or likely related to TTX-030 as a single agent, or the combination of TTX-030 and other agent(s), and met the following criteria: NCI CTCAE Version 5.0 Grade 5 event, Grade 4 hematological or Grade≥3 non-hematological toxicities, or Grade≥3 irAEs. Laboratory abnormalities that were asymptomatic and deemed not clinically significant were not regarded as DLTs. During Dose Escalation, each dosing cohort was completed through the DLT observation window before escalation was allowed within its arm. In each Safety Lead-in cohort, all participants were closely monitored for the occurrence of DLTs.
Objective Response Rate (ORR) - Arm 1 and Arm 2 Expansion CohortsThrough study completion, an average of 1 yearAnti-tumor activity in subjects treated with TTX-030 as single agent or in combination with specified regimens

Secondary

MeasureTime frameDescription
Maximum Plasma Concentration (Cmax)Cycles 1-3 (each cycle is 21-28 days)PK parameters of serum TTX-030 by Arm and Dose - Cycle 1
Objective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)Through study completion, an average of 1 yearAnti-tumor activity in subjects treated with TTX-030 as single agent or in combination with specified regimens

Countries

United States

Participant flow

Participants by arm

ArmCount
Arm 1: TTX-030 0.5 mg/kg
Participants in Arm 1 Escalation were administered IV 0.5 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
1
Arm 1: TTX-030 1.5 mg/kg
Participants in Arm 1 Escalation were administered IV 1.5 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
2
Arm 1: TTX-030 3.0 mg/kg
Participants in Arm 1 Escalation were administered IV 3 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
2
Arm 1: TTX-030 6.0 mg/kg
Participants in Arm 1 Escalation were administered IV 6 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
4
Arm 1: TTX-030 10 mg/kg
Participants in Arm 1 Escalation were administered IV 10mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
3
Arm 1: TTX-030 20 mg/kg
Participants in Arm 1 Escalation were administered IV 20 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
3
Arm 1: TTX-030 40 mg/kg
Participants in Arm 1 Escalation were administered IV 40 mg/kg dose of TTX-030 Q3W on the first day of each 21-day treatment cycle.
6
Arm 1 Expansion: TTX-030 40 mg/kg Load/30 mg/kg Q3W
Participants in Expansion received TTX-030 IV loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W.
8
Arm 2 (Safety Lead-in and Expansion), Combination
Participants in Safety Lead-in portion and Expansion of Arm 2 received TTX-030 IV loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W and pembrolizumab IV at a dose of 200 mg on Day 1 of each 21-day treatment cycle.
13
Arm 4 (Safety Lead-In and Expansion)
Participants in Safety Lead-in and Arm 4 received TTX-030 IV loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W and received gemcitabine 1000 mg/m\^2 + nab-Paclitaxel 125 mg/m\^2 Days 1, 8, and 15 every 28 days.
14
Total56

Baseline characteristics

CharacteristicTotalArm 1: TTX-030 3.0 mg/kgArm 1: TTX-030 1.5 mg/kgArm 1: TTX-030 6.0 mg/kgArm 1: TTX-030 10 mg/kgArm 1: TTX-030 20 mg/kgArm 1: TTX-030 40 mg/kgArm 1 Expansion: TTX-030 40 mg/kg Load/30 mg/kg Q3WArm 2 (Safety Lead-in and Expansion), CombinationArm 1: TTX-030 0.5 mg/kgArm 4 (Safety Lead-In and Expansion)
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
25 Participants1 Participants2 Participants2 Participants1 Participants1 Participants2 Participants4 Participants4 Participants0 Participants8 Participants
Age, Categorical
Between 18 and 65 years
31 Participants1 Participants0 Participants2 Participants2 Participants2 Participants4 Participants4 Participants9 Participants1 Participants6 Participants
Age, Continuous63.5 years59.5 years73 years63 years64 years59 years61.5 years64.5 years57 years26 years66.5 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Black or African American
6 Participants0 Participants1 Participants0 Participants1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants3 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants
Race (NIH/OMB)
White
45 Participants2 Participants1 Participants3 Participants2 Participants2 Participants6 Participants6 Participants12 Participants1 Participants10 Participants
Region of Enrollment
United States
56 participants2 participants2 participants4 participants3 participants3 participants6 participants8 participants13 participants1 participants14 participants
Sex: Female, Male
Female
34 Participants2 Participants1 Participants3 Participants3 Participants1 Participants2 Participants5 Participants6 Participants1 Participants10 Participants
Sex: Female, Male
Male
22 Participants0 Participants1 Participants1 Participants0 Participants2 Participants4 Participants3 Participants7 Participants0 Participants4 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
deaths
Total, all-cause mortality
0 / 11 / 21 / 21 / 41 / 32 / 33 / 61 / 84 / 137 / 14
other
Total, other adverse events
1 / 11 / 22 / 24 / 43 / 33 / 33 / 66 / 813 / 1314 / 14
serious
Total, serious adverse events
0 / 11 / 21 / 21 / 41 / 30 / 34 / 62 / 86 / 134 / 14

Outcome results

Primary

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

A DLT was defined as any clinically significant AE that occurred during Treatment Cycle 1 that the Investigator or Sponsor considered as possibly or likely related to TTX-030 as a single agent, or the combination of TTX-030 and other agent(s), and met the following criteria: NCI CTCAE Version 5.0 Grade 5 event, Grade 4 hematological or Grade≥3 non-hematological toxicities, or Grade≥3 irAEs. Laboratory abnormalities that were asymptomatic and deemed not clinically significant were not regarded as DLTs. During Dose Escalation, each dosing cohort was completed through the DLT observation window before escalation was allowed within its arm. In each Safety Lead-in cohort, all participants were closely monitored for the occurrence of DLTs.

Time frame: 1 cycle (each cycle is 21-28 days)

Population: All participants in the Dose Escalation cohorts who received 1 infusion during the treatment cycle and completed safety evaluations through the end of the DLT period or experienced a DLT before the end of the DLT period (ie, participants started Cycle 2 or experienced a DLT).

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Arm 1: TTX-030 1.5 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Arm 1: TTX-030 3.0 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Arm 1: TTX-030 6.0 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Arm 1: TTX-030 10 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Arm 1: TTX-030 20 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Arm 1: TTX-030 40 mg/kgNumber of Participants Who Experienced Dose-Limiting Toxicities (DLTs)0 Participants
Primary

Objective Response Rate (ORR) - Arm 1 and Arm 2 Expansion Cohorts

Anti-tumor activity in subjects treated with TTX-030 as single agent or in combination with specified regimens

Time frame: Through study completion, an average of 1 year

Population: Participants in the Safety Analysis Set who had at least 1 post baseline evaluable tumor assessment unless death or clinical progressive disease (PD) occurred before the first post baseline disease assessment.

ArmMeasureValue (NUMBER)
Arm 1: TTX-030 1.5 mg/kgObjective Response Rate (ORR) - Arm 1 and Arm 2 Expansion Cohorts7 percentage of participants
Arm 1: TTX-030 3.0 mg/kgObjective Response Rate (ORR) - Arm 1 and Arm 2 Expansion Cohorts9.1 percentage of participants
Secondary

Maximum Plasma Concentration (Cmax)

PK parameters of serum TTX-030 by Arm and Dose - Cycle 1

Time frame: Cycles 1-3 (each cycle is 21-28 days)

Population: Dose-Normalized PK Parameters of Serum TTX-030

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Arm 1: TTX-030 1.5 mg/kgMaximum Plasma Concentration (Cmax)4.91 Cmax (μg/mL)Geometric Coefficient of Variation 0
Arm 1: TTX-030 3.0 mg/kgMaximum Plasma Concentration (Cmax)25.9 Cmax (μg/mL)Geometric Coefficient of Variation 8.2
Arm 1: TTX-030 6.0 mg/kgMaximum Plasma Concentration (Cmax)35.2 Cmax (μg/mL)Geometric Coefficient of Variation 6.4
Arm 1: TTX-030 10 mg/kgMaximum Plasma Concentration (Cmax)79.3 Cmax (μg/mL)Geometric Coefficient of Variation 49.3
Arm 1: TTX-030 20 mg/kgMaximum Plasma Concentration (Cmax)188 Cmax (μg/mL)Geometric Coefficient of Variation 13.8
Arm 1: TTX-030 40 mg/kgMaximum Plasma Concentration (Cmax)190 Cmax (μg/mL)Geometric Coefficient of Variation 75.8
Arm 1: TTX-030 40 mg/kgMaximum Plasma Concentration (Cmax)629 Cmax (μg/mL)Geometric Coefficient of Variation 47.6
Arm 4 (Safety Lead-In and Expansion)Maximum Plasma Concentration (Cmax)694 Cmax (μg/mL)Geometric Coefficient of Variation 56.8
Arm 2 (Safety Lead-in and Expansion), CombinationMaximum Plasma Concentration (Cmax)647 Cmax (μg/mL)Geometric Coefficient of Variation 50.5
Arm 4 (Safety Lead-In and Expansion)Maximum Plasma Concentration (Cmax)487 Cmax (μg/mL)Geometric Coefficient of Variation 27.3
Secondary

Objective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)

Anti-tumor activity in subjects treated with TTX-030 as single agent or in combination with specified regimens

Time frame: Through study completion, an average of 1 year

Population: Participants in the Safety Analysis Set who had at least 1 post baseline evaluable tumor assessment unless death or clinical progressive disease (PD) occurred before the first post baseline disease assessment.

ArmMeasureValue (NUMBER)
Arm 1: TTX-030 1.5 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)1 percentage of participants
Arm 1: TTX-030 3.0 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)2 percentage of participants
Arm 1: TTX-030 6.0 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)1 percentage of participants
Arm 1: TTX-030 10 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)3 percentage of participants
Arm 1: TTX-030 20 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)2 percentage of participants
Arm 1: TTX-030 40 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)3 percentage of participants
Arm 1: TTX-030 40 mg/kgObjective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)6 percentage of participants
Arm 4 (Safety Lead-In and Expansion)Objective Response Rate (ORR) (Except for Arm 1 and 2 Expansion Cohorts, Where ORR Was a Primary Endpoint)30.8 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026