Solid Tumor, Adult
Conditions
Keywords
Gastric (gastroesophageal cancer), Advanced Solid Tumor, Colorectal cancer, Cancer, Metastatic Solid Tumor, Combination Therapy, CD39, Adenosine Pathway, Immunotherapy Immuno-oncology, PD-1 Checkpoint Inhibitor, Docetaxel, Budigalimab, ABBV-181, TTX-030, Non-small cell lung cancer, Urothelial cell cancer, Pancreatic cancer, Pembrolizumab, Keytruda, Bladder cancer, Gemcitabine, Nab-paclitaxel
Brief summary
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.
Interventions
COMBINATION_PRODUCTTTX-030, budigalimab and mFOLFOX6
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030, budigalimab and docetaxel
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030 and mFOLFOX6
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030 and budigalimab
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030, budigalimab, nab-paclitaxel and gemcitabine
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030 and pembrolizumab
Dose and schedule per protocol
COMBINATION_PRODUCTTTX-030, nab-paclitaxel and gemcitabine
Dose and schedule per protocol
COMBINATION_PRODUCTBudigalimab and mFOLFOX6
Dose and schedule per protocol
Sponsors
AbbVie
Trishula Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 7 day load + 1 cycle (1 cycle is 28 days) | A DLT was defined as the occurrence of any of the following toxicities within the DLT Evaluation Period if judged by the Investigator and Sponsor to be possibly, probably, or definitely related to TTX-030 or budigalimab. |
| The Incident of Adverse Events | Through study completion, an average of 1 year | Number of study subjects experiencing adverse events (AEs) and serious adverse events (SAEs). Safety profile will be assessed through laboratory evaluations, vital signs, and physical examinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Through study completion, an average of 1 year | 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. |
| Disease Control Rate (DCR) | Through study completion, an average of 1 year | DCR is defined as the proportion of subjects with CR, PR, or SD per RECIST 1.1 |
| Confirmed Objective Response Rate (ORR) | Through study completion, an average of 1 year | ORR is defined as the proportion of subjects with CR or PR. |
| Overall Survival (OS) | Through study completion, an average of 1 year | OS was defined as the time interval from the first dose of study treatment to death from any cause. Participants who were lost to follow-up or survived until the end of the study were censored at the last date that they were known to be alive. Medians, Q1, and Q3 of OS and the proportion of participants who were alive at 3, 6, 9, and 12 months from Study Day 1 were derived using KM methods. |
| Pharmacokinetics (PK) | Cycles 1-4 (each cycle is 21-28 days) | Serum concentrations of TTX-030 will be tabulated |
| Progression-free Survival (PFS) | Through study completion, an average of 1 year | PFS is measured from documentation of progression or death from any cause, whichever occurs first |
| Best Response (BOR) | Through study completion, an average of 1 year | The BOR was defined as the best response (in the order of CR, PR, stable disease, and PD) by RECIST 1.1 documented from first dose until the end of study, first disease progression, death, or start of new anticancer therapy, whichever was earliest. |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) Participants in Cohort 1 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W on Days 1 and 15, plus budigalimab at a dose of 500 mg (Q4W) on Day 1 plus mFOLFOX6 over 48 hours (Q2W) on Day 1 and 15 of each 28-day cycle. | 8 |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) Participants in Cohort 3B were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W on Days 1 and 15, plus budigalimab at a dose of 500 mg (Q4W) on Day 1 plus mFOLFOX6 over 48 hours (Q2W) on Day 1 and 15 of each 28-day cycle. | 44 |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6 Participants in Cohort 12 were administered IV budigalimab at a dose of 500 mg (Q4W) on Day 1 plus mFOLFOX6 over 48 hours (Q2W) on Day 1 and 15 of each 28-day cycle. | 25 |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) Participants in Cohort 3A were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W on Days 1 and 15 plus mFOLFOX6 over 48 hours (Q2W) on Day 1 and 15 of each 28-day cycle. | 6 |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) Participants in Safety Lead-in Cohort 2 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W plus budigalimab 375 mg Q3W plus docetaxel at a dose of 75 mg/m2 Q3W on Day 1 of each 21-day treatment cycle. | 7 |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) Participants in Cohort 9 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W on Days 1 and 15 plus budigalimab at a dose of 500 mg (Q4W) on Day 1 plus gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on Days 1, 8, and 15 each 28-day cycle. | 28 |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) Participants in Cohort 11 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 20 mg/kg Q2W on Days 1 and 15 plus gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on Days 1, 8, and 15 each 28-day cycle. | 17 |
| Cohort 4 - CRC (TTX-030 + Budigalimab) Participants in Cohort 4 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W plus budigalimab at a dose of 375 mg Q3W on Day 1 of each 21-day treatment cycle. | 14 |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) Participants in Cohort 6 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W plus budigalimab at a dose of 375 mg Q3W on Day 1 of each 21-day treatment cycle. | 5 |
| Cohort 8 - GEC (TTX-030 + Budigalimab) Participants in Cohort 8 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W plus budigalimab at a dose of 375 mg Q3W on Day 1 of each 21-day treatment cycle. | 23 |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) Participants in Cohort 10 were administered IV TTX-030 at a loading dose of 40 mg/kg 7 days before Cycle 1 Day 1 followed by treatment with 30 mg/kg Q3W plus pembrolizumab at a dose of 200 mg Q3W on Day 1 of each 21-day treatment cycle. | 8 |
| Total | 185 |
Baseline characteristics
| Characteristic | Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Cohort 12 - Gastric (Budigalimab + mFOLFOX6 | Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Cohort 4 - CRC (TTX-030 + Budigalimab) | Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Cohort 8 - GEC (TTX-030 + Budigalimab) | Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 11 Participants | 2 Participants | 3 Participants | 16 Participants | 11 Participants | 5 Participants | 2 Participants | 11 Participants | 4 Participants | 5 Participants | 83 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 14 Participants | 4 Participants | 4 Participants | 12 Participants | 6 Participants | 9 Participants | 3 Participants | 12 Participants | 4 Participants | 3 Participants | 102 Participants |
| Age, Continuous | 59.5 years STANDARD_DEVIATION 12.51 | 63.2 years STANDARD_DEVIATION 8.7 | 62.5 years STANDARD_DEVIATION 6.28 | 65.7 years STANDARD_DEVIATION 7.95 | 65.7 years STANDARD_DEVIATION 6.83 | 68.2 years STANDARD_DEVIATION 9.5 | 61.4 years STANDARD_DEVIATION 10.57 | 65.2 years STANDARD_DEVIATION 6.57 | 61 years STANDARD_DEVIATION 15.54 | 65.9 years STANDARD_DEVIATION 9.4 | 66.4 years STANDARD_DEVIATION 7.42 | 63.1 years STANDARD_DEVIATION 10.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 22 Participants | 2 Participants | 0 Participants | 9 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 69 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) White | 17 Participants | 3 Participants | 3 Participants | 6 Participants | 16 Participants | 12 Participants | 10 Participants | 3 Participants | 17 Participants | 7 Participants | 5 Participants | 99 Participants |
| Region of Enrollment South Korea | 24 Participants | 21 Participants | 2 Participants | 0 Participants | 8 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 61 Participants |
| Region of Enrollment United States | 20 Participants | 4 Participants | 4 Participants | 7 Participants | 20 Participants | 15 Participants | 14 Participants | 4 Participants | 23 Participants | 8 Participants | 5 Participants | 124 Participants |
| Sex: Female, Male Female | 18 Participants | 1 Participants | 2 Participants | 0 Participants | 13 Participants | 6 Participants | 5 Participants | 1 Participants | 8 Participants | 2 Participants | 1 Participants | 57 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 4 Participants | 7 Participants | 15 Participants | 11 Participants | 9 Participants | 4 Participants | 15 Participants | 6 Participants | 7 Participants | 128 Participants |
Adverse events
| Event type | EG000 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 | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 13 / 44 | 7 / 25 | 2 / 6 | 0 / 7 | 11 / 28 | 8 / 17 | 7 / 14 | 2 / 5 | 10 / 23 | 2 / 8 |
| other Total, other adverse events | 8 / 8 | 43 / 44 | 25 / 25 | 6 / 6 | 7 / 7 | 28 / 28 | 17 / 17 | 14 / 14 | 1 / 5 | 23 / 23 | 8 / 8 |
| serious Total, serious adverse events | 4 / 8 | 27 / 44 | 16 / 25 | 2 / 6 | 4 / 7 | 16 / 28 | 8 / 17 | 4 / 14 | 2 / 5 | 10 / 23 | 3 / 8 |
Outcome results
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT was defined as the occurrence of any of the following toxicities within the DLT Evaluation Period if judged by the Investigator and Sponsor to be possibly, probably, or definitely related to TTX-030 or budigalimab.
Time frame: 7 day load + 1 cycle (1 cycle is 28 days)
Population: Only Cohort 1 and Cohort 2 are the safety lead-in cohorts and were evaluated for DLTs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 6 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 7 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
The Incident of Adverse Events
Number of study subjects experiencing adverse events (AEs) and serious adverse events (SAEs). Safety profile will be assessed through laboratory evaluations, vital signs, and physical examinations.
Time frame: Through study completion, an average of 1 year
Population: This set included all participants who received at least 1 dose or any partial dose of study treatment. The Safety Analysis Set was used for safety endpoints and study treatment administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | The Incident of Adverse Events | 8 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | The Incident of Adverse Events | 44 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | The Incident of Adverse Events | 25 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | The Incident of Adverse Events | 6 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | The Incident of Adverse Events | 7 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | The Incident of Adverse Events | 28 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | The Incident of Adverse Events | 17 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | The Incident of Adverse Events | 14 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | The Incident of Adverse Events | 5 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | The Incident of Adverse Events | 23 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | The Incident of Adverse Events | 8 Participants |
Secondary
Best Response (BOR)
The BOR was defined as the best response (in the order of CR, PR, stable disease, and PD) by RECIST 1.1 documented from first dose until the end of study, first disease progression, death, or start of new anticancer therapy, whichever was earliest.
Time frame: Through study completion, an average of 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | NE | 1 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | Stable Disease | 2 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | PR | 1 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | CR | 0 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | PD | 3 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | CR | 5 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | PD | 2 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | Stable Disease | 14 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | PR | 18 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Best Response (BOR) | NE | 2 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Best Response (BOR) | Stable Disease | 6 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Best Response (BOR) | NE | 0 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Best Response (BOR) | PR | 14 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Best Response (BOR) | CR | 2 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Best Response (BOR) | PD | 1 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Best Response (BOR) | CR | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Best Response (BOR) | PR | 3 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Best Response (BOR) | NE | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Best Response (BOR) | Stable Disease | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Best Response (BOR) | PD | 1 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Best Response (BOR) | CR | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Best Response (BOR) | PR | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Best Response (BOR) | Stable Disease | 7 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Best Response (BOR) | PD | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Best Response (BOR) | NE | 0 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | PR | 9 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | PD | 3 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | NE | 2 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | Stable Disease | 13 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | CR | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | Stable Disease | 10 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | NE | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | CR | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | PR | 4 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Best Response (BOR) | PD | 3 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Best Response (BOR) | PR | 0 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Best Response (BOR) | Stable Disease | 3 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Best Response (BOR) | PD | 8 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Best Response (BOR) | CR | 0 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Best Response (BOR) | NE | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Best Response (BOR) | NE | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Best Response (BOR) | PR | 0 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Best Response (BOR) | CR | 0 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Best Response (BOR) | PD | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Best Response (BOR) | Stable Disease | 3 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Best Response (BOR) | CR | 1 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Best Response (BOR) | PD | 11 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Best Response (BOR) | NE | 4 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Best Response (BOR) | Stable Disease | 5 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Best Response (BOR) | PR | 1 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Best Response (BOR) | CR | 1 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Best Response (BOR) | PD | 5 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Best Response (BOR) | PR | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Best Response (BOR) | NE | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Best Response (BOR) | Stable Disease | 2 Participants |
Secondary
Confirmed Objective Response Rate (ORR)
ORR is defined as the proportion of subjects with CR or PR.
Time frame: Through study completion, an average of 1 year
Population: The ORR was defined as the proportion of participants who achieved a BOR of either CR or PR as derived based on the lesion measurement provided by the Investigator per RECIST v1.1. Confirmed ORR was defined as 2 disease response assessments showing objective response (CR or PR) at least 4 weeks apart and was presented with corresponding 2-sided 95% confidence intervals (CIs) based on the Clopper-Pearson method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Confirmed Objective Response Rate (ORR) | 14.3 percentage of participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Confirmed Objective Response Rate (ORR) | 56.1 percentage of participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Confirmed Objective Response Rate (ORR) | 69.6 percentage of participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Confirmed Objective Response Rate (ORR) | 75.0 percentage of participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Confirmed Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Confirmed Objective Response Rate (ORR) | 33.3 percentage of participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Confirmed Objective Response Rate (ORR) | 23.5 percentage of participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Confirmed Objective Response Rate (ORR) | 0.0 percentage of participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Confirmed Objective Response Rate (ORR) | 0.0 percentage of participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Confirmed Objective Response Rate (ORR) | 9.1 percentage of participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Confirmed Objective Response Rate (ORR) | 12.5 percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects with CR, PR, or SD per RECIST 1.1
Time frame: Through study completion, an average of 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Disease Control Rate (DCR) | 3 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Disease Control Rate (DCR) | 37 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Disease Control Rate (DCR) | 22 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Disease Control Rate (DCR) | 3 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Disease Control Rate (DCR) | 2 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Disease Control Rate (DCR) | 22 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Disease Control Rate (DCR) | 14 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Disease Control Rate (DCR) | 3 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Disease Control Rate (DCR) | 1 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Disease Control Rate (DCR) | 7 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Disease Control Rate (DCR) | 1 Participants |
Secondary
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.
Time frame: Through study completion, an average of 1 year
Population: Number (%) of subjects with events (PFS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Duration of Response (DOR) | 13 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Duration of Response (DOR) | 4 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Duration of Response (DOR) | 3 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Duration of Response (DOR) | 4 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Duration of Response (DOR) | 4 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Duration of Response (DOR) | 1 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Duration of Response (DOR) | 0 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time interval from the first dose of study treatment to death from any cause. Participants who were lost to follow-up or survived until the end of the study were censored at the last date that they were known to be alive. Medians, Q1, and Q3 of OS and the proportion of participants who were alive at 3, 6, 9, and 12 months from Study Day 1 were derived using KM methods.
Time frame: Through study completion, an average of 1 year
Population: Participants with events (death)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | Participants censored | 5 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | PD | 1 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | Participants censored | 28 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | Other | 0 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Overall Survival (OS) | PD | 13 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Overall Survival (OS) | PD | 4 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Overall Survival (OS) | AE | 3 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Overall Survival (OS) | Participants censored | 16 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Overall Survival (OS) | Other | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Overall Survival (OS) | PD | 1 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Overall Survival (OS) | Participants censored | 2 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Overall Survival (OS) | Other | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Overall Survival (OS) | PD | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Overall Survival (OS) | Participants censored | 7 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | AE | 1 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | Participants censored | 16 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | PD | 9 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | Participants censored | 9 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | PD | 8 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Overall Survival (OS) | Other | 0 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Overall Survival (OS) | PD | 6 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Overall Survival (OS) | Participants censored | 5 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Overall Survival (OS) | PD | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Overall Survival (OS) | Participants censored | 3 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Overall Survival (OS) | Other | 1 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Overall Survival (OS) | PD | 8 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Overall Survival (OS) | AE | 1 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Overall Survival (OS) | Participants censored | 12 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Overall Survival (OS) | Other | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Overall Survival (OS) | AE | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Overall Survival (OS) | Participants censored | 7 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Overall Survival (OS) | PD | 1 Participants |
Secondary
Pharmacokinetics (PK)
Serum concentrations of TTX-030 will be tabulated
Time frame: Cycles 1-4 (each cycle is 21-28 days)
Population: Pharmacokinetic Parameters of Serum TTX-030 by Treatment and Visit at C1D1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Pharmacokinetics (PK) | 503 (ug/mL) | Geometric Coefficient of Variation 39.1 |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Pharmacokinetics (PK) | 449 (ug/mL) | Geometric Coefficient of Variation 24.1 |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Pharmacokinetics (PK) | 814 (ug/mL) | Geometric Coefficient of Variation 26.4 |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Pharmacokinetics (PK) | 511 (ug/mL) | Geometric Coefficient of Variation 28.1 |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Pharmacokinetics (PK) | 458 (ug/mL) | Geometric Coefficient of Variation 15.5 |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Pharmacokinetics (PK) | 601 (ug/mL) | Geometric Coefficient of Variation 41.3 |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Pharmacokinetics (PK) | 679 (ug/mL) | Geometric Coefficient of Variation 31.3 |
Secondary
Progression-free Survival (PFS)
PFS is measured from documentation of progression or death from any cause, whichever occurs first
Time frame: Through study completion, an average of 1 year
Population: Participants with events (PFS) by Investigator
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Participants censored | 1 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Death | 1 Participants |
| Cohort 1 - Safety Lead-in (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | PD | 5 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Participants censored | 12 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Death | 2 Participants |
| Cohort 3B - Gastric (TTX-030 + Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | PD | 27 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Death | 3 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | PD | 9 Participants |
| Cohort 12 - Gastric (Budigalimab + mFOLFOX6) | Progression-free Survival (PFS) | Participants censored | 11 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Progression-free Survival (PFS) | Death | 0 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Progression-free Survival (PFS) | PD | 4 Participants |
| Cohort 3A - Gastric (TTX-030 + mFOLFOX6) | Progression-free Survival (PFS) | Participants censored | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Progression-free Survival (PFS) | Death | 0 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Progression-free Survival (PFS) | Participants censored | 4 Participants |
| Cohort 2 - mCRPC (TTX-030 + Budigalimab + Docetaxel) | Progression-free Survival (PFS) | PD | 3 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | Participants censored | 8 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | PD | 14 Participants |
| Cohort 9 - Pancreatic (TTX-030 + Budigalimab + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | Death | 5 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | Participants censored | 0 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | Death | 2 Participants |
| Cohort 11 - Pancreatic (TTX-030 + Gemcitabine + Nab-Paclitaxel) | Progression-free Survival (PFS) | PD | 15 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | PD | 10 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Participants censored | 1 Participants |
| Cohort 4 - CRC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Death | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Death | 1 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | PD | 3 Participants |
| Cohort 6 - HNSCC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Participants censored | 1 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | PD | 17 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Death | 2 Participants |
| Cohort 8 - GEC (TTX-030 + Budigalimab) | Progression-free Survival (PFS) | Participants censored | 3 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Progression-free Survival (PFS) | Death | 0 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Progression-free Survival (PFS) | PD | 6 Participants |
| Cohort 10 - UCC (TTX-030 + Pembrolizumab) | Progression-free Survival (PFS) | Participants censored | 2 Participants |