TTX-030 + Chemotherapy for Pancreatic Cancer

Recruiting at 58 trial locations

Overseen By Trishula Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trishula Therapeutics, Inc.

Must be taking: Chemotherapy

Must not be taking: Investigational agents, Live vaccines

Disqualifiers: Autoimmune disease, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

194 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are using an investigational agent, you must stop it at least 14 days before starting the trial.

What data supports the effectiveness of the drug TTX-030 + Chemotherapy for Pancreatic Cancer?

The research suggests that combining different drugs can enhance the immune system's ability to fight pancreatic cancer. For example, combining CXCR4 blockers with PD-1 inhibitors showed promise in improving patient outcomes, which may indicate potential benefits for similar combination therapies like TTX-030 with chemotherapy. ^{1 2 3 4 5}

What safety information is available for TTX-030 and similar treatments?

Immune checkpoint inhibitors, like TTX-030, can cause immune-related side effects, especially in the digestive system, such as inflammation of the colon (colitis) and liver issues. These side effects can range from mild to severe, and women and those on multiple therapies may be at higher risk. It's important to monitor for these side effects and manage them with appropriate treatments, such as steroids, if they occur. ^{6 7 8 9 10}

What makes the drug TTX-030 + Chemotherapy unique for pancreatic cancer?

TTX-030 combined with chemotherapy for pancreatic cancer is unique because it involves Budigalimab, a novel component not typically used in standard treatments like nab-paclitaxel or gemcitabine. This combination may offer a new mechanism of action or improved effectiveness compared to existing therapies. ^{11 12 13 14 15}

What is the purpose of this trial?

This is a Phase 2, multicenter, open-label, 3-arm, randomized, parallel group study to evaluate the efficacy and safety of TTX-030 with or without budigalimab in combination with chemotherapy (gemcitabine + nab-paclitaxel) in subjects with metastatic PDAC who did not have prior treatment for metastatic disease and are eligible to receive gemcitabine and nab-paclitaxel chemotherapy as SOC.

Eligibility Criteria

This trial is for adults over 18 with metastatic pancreatic cancer (mPDAC) who haven't had treatment for their advanced disease yet. They should be able to receive standard chemotherapy and have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

Evidence of measurable disease per RECIST 1.1

My cancer is a type of pancreatic cancer that has spread.

I haven't had any systemic treatment for my metastatic disease.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

I have not received a live vaccine in the last 28 days.

History of clinically significant allergy or hypersensitivity to planned study treatment components or to any monoclonal antibody

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TTX-030 with or without budigalimab in combination with chemotherapy (gemcitabine + nab-paclitaxel)

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Budigalimab
• TTX-030

Trial Overview The study tests TTX-030 combined with standard chemo (nab-paclitaxel and gemcitabine), both with and without another drug called budigalimab, against just the chemo alone. It's to see which combination works best for treating mPDAC.

Participant Groups

Group I: Arm 2 Experimental Treatment 1 Intervention

TTX-030 plus budigalimab plus nab-paclitaxel and gemcitabine

Group II: Arm 1 Experimental Treatment 1 Intervention

TTX-030 plus nab-paclitaxel and gemcitabine

Group III: Arm 3 Active Control 1 Intervention

Nab-Paclitaxel and gemcitabine

Who Is Running the Clinical Trial?

Trishula Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

440+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a phase Ib trial involving 22 patients with metastatic pancreatic ductal adenocarcinoma, combinations of avelumab or talazoparib with binimetinib showed higher-than-expected rates of dose-limiting toxicity (DLT), particularly at the 45 mg dose, leading to dose adjustments.

Despite the safety concerns, the overall safety profiles of the combinations were consistent with those of the individual drugs, but no objective tumor responses were observed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. Rodon Ahnert, J., Tan, DS., Garrido-Laguna, I., et al.[2023]

In a phase IIa study involving 59 patients with metastatic pancreatic ductal adenocarcinoma (PDAC), the CXCR4 antagonist BL-8040 combined with pembrolizumab showed a disease control rate of 34.5% in chemotherapy-resistant patients, with a median overall survival of 3.3 months, and 7.5 months for those receiving it as second-line therapy.

When BL-8040 was combined with pembrolizumab and chemotherapy, the treatment resulted in an objective response rate of 32% and a disease control rate of 77%, indicating that this combination may enhance the effectiveness of chemotherapy in PDAC and should be further investigated in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Bockorny, B., Semenisty, V., Macarulla, T., et al.[2021]

A study analyzing 70,330 adverse events reported to the FDA found that immune checkpoint inhibitors (ICIs) significantly increase the risk of gastrointestinal (GI) toxicities, particularly colitis, hepatobiliary disorders, and pancreatitis, with colitis showing the highest reporting odds ratio of 17.2.

The risk of these GI adverse events was notably higher with anti-CTLA-4 treatments compared to anti-PD-1 and anti-PD-L1 therapies, and factors such as female gender and polytherapy were identified as strong risk factors for these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. Bai, X., Jiang, S., Zhou, Y., et al.[2021]

Two melanoma patients experienced rare neurological immune-related adverse events (irAEs) after treatment with ipilimumab, including meningoencephalomyelitis and acute inflammatory demyelinating polyneuropathy (AIDP).

Both patients responded well to treatment with immunosuppressive therapies, highlighting the importance of early recognition and intervention for neurological irAEs to prevent long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. Garcia, CA., El-Ali, A., Rath, TJ., et al.[2019]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

In a phase 1 study involving 9 patients with locally advanced pancreatic cancer, the combination of weekly nab-paclitaxel and daily radiotherapy was found to be safe and well-tolerated, with minimal severe side effects.

After treatment, 4 patients were able to undergo surgical resection with negative margins, indicating a significant treatment effect and limited tumor viability, suggesting potential for improved outcomes in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Shabason, JE., Chen, J., Apisarnthanarax, S., et al.[2022]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

An immune-related gene prognostic risk index for pancreatic adenocarcinoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Comprehensive immunoprofile analysis of prognostic markers in pancreaticobiliary tract cancers. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

The Novel, Orally Bioavailable CDK9 Inhibitor Atuveciclib Sensitises Pancreatic Cancer Cells to TRAIL-induced Cell Death. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Advances in the Genetic Screening, Work-up, and Treatment of Pancreatic Cancer. [2020]

13. Germany pubmed.ncbi.nlm.nih.gov

A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination. [2022]

14. Germany pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]