LSTA1 + Standard Treatment for Pancreatic Cancer

(FORTIFIDE Trial)

No longer recruiting at 4 trial locations

Overseen By Kathryn Shantz

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lisata Therapeutics, Inc.

Must be taking: Nab-paclitaxel, Gemcitabine

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Infection, Hepatitis, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Ongoing with cycles every 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called LSTA1 (also known as CEND-1 or IRGD) combined with standard chemotherapy for treating metastatic pancreatic cancer. The goal is to determine if adding LSTA1 enhances the safety and effectiveness of the treatment compared to standard chemotherapy alone. Participants must visit the clinic for treatment and tests three times every 28 days and undergo scans every 8 weeks. Those with untreated metastatic pancreatic cancer, eligible for certain chemotherapy drugs, and maintaining a good level of daily activity might be suitable for this study. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you do not use any other anti-cancer therapy while participating. However, it does not specify about other types of medications, so you should discuss your current medications with the trial team.

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

Research has shown that LSTA1, also known as certepetide, has been safe in earlier studies. In these studies, patients with metastatic pancreatic cancer who took LSTA1 with standard treatments did not experience unexpected or severe side effects from the new drug. Most side effects resulted from the cancer itself or were typical of standard chemotherapy.

Some deaths occurred in the studies, mostly due to cancer progression or other causes, such as a stroke. This indicates that the treatment is generally well-tolerated and does not introduce significant new risks.

Overall, the treatment has been tested in various studies and is considered to have a manageable safety profile. However, as with any clinical trial, participants should discuss potential risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LSTA1 for pancreatic cancer because it introduces certepetide, a novel ingredient that could enhance the effectiveness of standard chemotherapy. Unlike current treatments that primarily focus on killing cancer cells, LSTA1, through its certepetide component, might improve how the body responds to chemotherapy by targeting the tumor's environment. This could potentially lead to more effective shrinking of tumors and better patient outcomes. Additionally, the use of certepetide in combination with standard chemotherapy is being explored in different dosages and delivery methods, which might offer more personalized treatment options for patients.

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

Studies have shown promising results for the new drug LSTA1, also known as certepetide, in treating advanced pancreatic cancer. Research indicates that 59% of patients experienced a significant reduction in tumor size, including one patient whose cancer became undetectable and 16 others who saw a noticeable decrease. Additionally, another study found that 70% of patients had their tumors shrink partially after treatment. In this trial, participants will receive either standard chemotherapy alone or standard chemotherapy combined with LSTA1. These findings suggest that LSTA1, when used with standard chemotherapy, could be more effective than chemotherapy alone in reducing pancreatic tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Kristen K. Buck, MD

Principal Investigator

Lisata Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic cancer that has spread and can't be surgically removed. They should have a certain level of fitness (able to carry out light activities), expect to live at least 3 more months, have tumors measurable by scans, proper organ function, and must use birth control. Only those who've had specific first-line chemotherapy but the cancer got worse can join.

Inclusion Criteria

My organs and bone marrow are working well.

My pancreatic cancer cannot be removed with surgery.

I am using effective birth control methods.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Run-in

Participants receive LSTA1 or placebo components of their randomized treatment regimen

3 days

Treatment

Participants receive the study treatment with LSTA1 or placebo added to standard of care

Ongoing with cycles every 28 days

3 visits every 28 days

End-of-treatment Follow-up

Participants have an end-of-treatment follow-up visit

1 visit

Long-term Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after treatment discontinuation

What Are the Treatments Tested in This Trial?

Interventions

• LSTA1

Trial Overview The study is testing LSTA1 combined with standard chemo drugs Gemcitabine and Nab-paclitaxel against just the chemo drugs alone in patients with metastatic pancreatic ductal adenocarcinoma. It's checking if adding LSTA1 is safe, tolerable, and works better than current treatments.

How Is the Trial Designed?

Group I: SoC chemotherapy plus two certepetide IV pushes and placebo infusion Experimental Treatment 4 Interventions

Group II: SoC chemotherapy plus one certepetide IV push, one placebo IV push, and certepetide infusion Experimental Treatment 4 Interventions

Group III: SoC chemotherapy plus two placebo IV pushes and placebo infusion Active Control 3 Interventions

LSTA1 is already approved in United States, European Union for the following indications:

Approved in United States as LSTA1 for:

• Orphan drug designation for malignant glioma
• Orphan drug designation for osteosarcoma
• Fast track designation for pancreatic cancer

Approved in European Union as LSTA1 for:

• Orphan drug designation for pancreatic cancer

Who Is Running the Clinical Trial?

Lisata Therapeutics, Inc.

Lead Sponsor

Trials

17

Recruited

1,400+

Published Research Related to This Trial

CEND-1 (iRGD) shows a favorable pharmacokinetic profile, with a plasma half-life of about 2 hours in patients and significant retention in tumors for several hours after administration, indicating its potential for enhancing cancer treatment efficacy.

The study demonstrated that CEND-1 can improve tumor penetration and accumulation of anti-cancer agents, with effects lasting at least 24 hours in mouse models, suggesting it could significantly enhance the therapeutic index of co-administered treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Pharmacokinetics, Disposition, and Duration of Action of the Tumour-Targeting Peptide CEND-1. Järveläinen, HA., Schmithals, C., von Harten, M., et al.[2023]

Cyclic arginyl-glycyl-aspartic acid (cRGD) peptides enhance the delivery of cytotoxic agents by targeting αVβ3 integrin, which is overexpressed in many cancers, using ultrasmall gold nanoparticles (usGNPs).

The cRGD-functionalized usGNPs showed increased cellular uptake and cytotoxicity when loaded with mertansine, indicating improved efficacy and retention of the therapeutic payload in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload. Perrins, RD., McCarthy, LA., Robinson, A., et al.[2022]

The RAFT(cRGD)4 molecular conjugate vector effectively targets tumors by utilizing a cyclodecapeptide platform that enhances drug delivery and imaging capabilities, demonstrating significant tumor growth reduction in vivo with low doses.

This vector's design allows for specific targeting and internalization due to its multivalent presentation of cRGD motifs, making it a versatile tool for carrying multiple therapeutic agents and improving treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New multifunctional molecular conjugate vector for targeting, imaging, and therapy of tumors. Garanger, E., Boturyn, D., Jin, Z., et al.[2021]

The study developed new disulfide-bridged peptides, including LyP-1 and iRGD, that can be easily conjugated to anticancer agents, enhancing their delivery to tumor sites.

These conjugated peptides maintain their tumor-homing abilities and the biological activity of the attached drugs, potentially improving the effectiveness of targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor-Penetrating Peptides for Cancer Diagnosis and Treatment. Kotamraju, VR., Sharma, S., Kolhar, P., et al.[2020]

The RAFT-c(-RGDfK-)(4)-Cy5-SS-Q molecule effectively targets integrin alpha(V)beta(3) with improved specificity and allows for enhanced imaging of tumors by using a fluorescence quencher that only activates upon internalization.

This study demonstrated that the disulfide bond linking the quencher to the targeting vector is a successful strategy for delivering imaging agents intracellularly, as shown by significant fluorescence recovery in tumor cells after internalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo noninvasive optical imaging of receptor-mediated RGD internalization using self-quenched Cy5-labeled RAFT-c(-RGDfK-)(4). Jin, ZH., Razkin, J., Josserand, V., et al.[2016]

The addition of a cysteine residue to the tumor-targeting peptide iRGD significantly prolongs its plasma half-life, enhancing its effectiveness in delivering drugs into tumor tissue.

This modification allows for greater accumulation of therapeutic agents in tumors by facilitating the active transport of drugs across the vascular wall, improving the overall efficacy of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A free cysteine prolongs the half-life of a homing peptide and improves its tumor-penetrating activity. Pang, HB., Braun, GB., She, ZG., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e16274

Updated single institution outcome data from the first-in- ... Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.

2. ir.lisata.com ir.lisata.com/news-releases/news-release-details/lisata-therapeutics-announces-encouraging-preliminary-results

Press Release Details Based on these 10 patients, the R0 resection rate (no residual cancer at the surgical margins) was 50%, and 70% experienced a pathologic partial ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)42007-1/fulltext

1528P Phase I trial of the first-in-class agent CEND-1 in ... By investigator assessed RECIST 1.1 criteria, the overall response rate was 59%, one pt. with complete response (3.4%), 16 pts. with partial response (55%), 10 ...

4. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(22)00197-2/abstract

CEND-1: a game changer for pancreatic cancer ... In the USA there has been a small improvement in 5-year survival for all stages, increasing from approximately 5% to 11% in the past three decades, but this ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35803294/

Dual αV-integrin and neuropilin-1 targeting peptide CEND- ... In the efficacy population (n=29), 17 (59%) patients had an objective response, including one complete response and 16 partial responses.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2949819823000018

Trials in progress ASCEND: a randomised, double-blinded ... The aim of the ASCEND study is to investigate the activity, safety, and tolerability of LSTA1 in combination with first-line gemcitabine and nab-paclitaxel in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03517176

Study Details | NCT03517176 | CEND-1 in Combination ... This protocol is designed to evaluate the safety, tolerability, and biologic activity of CEND-1 in patients with metastatic pancreatic ductal adenocarcinoma ( ...