TTX-030 + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 67 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, TTX-030, with or without budigalimab (also known as ABBV-181), alongside standard chemotherapy for individuals with advanced pancreatic cancer. Researchers aim to determine if these combinations can improve outcomes for those who have not received prior treatment for their metastatic cancer. The study includes three groups: one receiving TTX-030 plus standard chemotherapy, another with TTX-030 and budigalimab plus chemotherapy, and a third group with only standard chemotherapy. The trial seeks participants with confirmed advanced pancreatic cancer who are suitable for the common chemotherapy drugs nab-paclitaxel and gemcitabine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments using TTX-030 have been promising in earlier studies. For instance, patients with advanced pancreatic cancer who received TTX-030 combinations lived longer on average. In one study with 57 patients, 30% responded well to the treatment, and some even experienced complete cancer remission. Importantly, the treatment was well-tolerated at the doses tested, as no maximum safe dose was identified.

When combined with another drug, budigalimab, studies have also assessed safety. So far, no major safety issues have emerged, suggesting that both TTX-030 alone and with budigalimab are generally safe. However, since this is a Phase 2 trial, monitoring for any side effects remains crucial as more information becomes available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which typically involve chemotherapy regimens like nab-paclitaxel and gemcitabine, the new investigational treatments introduce TTX-030 and budigalimab. TTX-030 is an innovative antibody that targets CD39, an enzyme that cancer cells use to evade the immune system, potentially boosting the body's natural ability to fight the tumor. Budigalimab, on the other hand, is an immune checkpoint inhibitor that may enhance the immune response against cancer cells. By combining these with traditional chemotherapy, researchers are hopeful these treatments will offer a more effective approach to tackling pancreatic cancer, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that TTX-030 may effectively treat advanced pancreatic cancer. Earlier studies found that 30% of patients responded to the treatment, with some experiencing complete recovery. On average, patients lived without cancer worsening for 7.5 months, and the average overall survival was 19.1 months. These findings suggest that TTX-030 could improve outcomes for patients with this challenging condition. In this trial, participants in one arm will receive TTX-030 combined with nab-paclitaxel and gemcitabine.

Researchers are also studying the combination of TTX-030 with budigalimab in another arm of this trial. Budigalimab is designed to work with TTX-030 by blocking certain proteins that help cancer cells survive. While more research is needed, early results for both treatments appear promising. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. prnewswire.com prnewswire.com/news-releases/trishula-therapeutics-presents-positive-results-from-phase-1-trial-of-ttx-030-in-first-line-metastatic-pancreatic-cancer-patients-302247474.html

Trishula Therapeutics Presents Positive Results from ... The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations.

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02244-0/fulltext

659P Combination treatment with TTX-030, a first-in-class ... For the overall efficacy-evaluable population (n=57), confirmed ORR was 30% with 3 complete responses, median PFS 7.5 months (95%CI 5.2, 9.4) and median OS 19.1 ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/trishula-positive-ttx-trial/

Trishula Therapeutics reports data from pancreatic cancer ... The results showed an objective response rate (ORR) of 30%, median progression-free survival of 7.5 months, and median overall survival of 19.1 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06119217

NCT06119217 | Phase 2 Study of TTX-030 and ... 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 ...

5. targetedonc.com targetedonc.com/view/phase-2-study-of-ttx-030-in-metastatic-pdac-begins

Phase 2 Study of TTX-030 in Metastatic PDAC Begins A phase 2 trial (NCT06119217) evaluating the safety and efficacy of TTX-030 as a first-line treatment for patients with metastatic pancreatic ductal ...

6. trishulatx.com trishulatx.com/news/press091624/

Press Release The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04306900

Study Details | NCT04306900 | TTX-030 in Combination ... This trial will study the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TTX-030 in combination with immunotherapy and/or ...