LSTA1 + Standard Treatment for Pancreatic Cancer

(FORTIFIDE Trial)

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

Trial Summary

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.

What data supports the effectiveness of the treatment LSTA1 for pancreatic cancer?

Research shows that CEND-1, a component of LSTA1, helps drugs reach tumors more effectively by improving their delivery and penetration into tumor tissues. This has been demonstrated in pre-clinical models and suggests that LSTA1 could enhance the effectiveness of standard treatments for pancreatic cancer by improving drug access to the tumor. ^{1 2 3 4 5}

Is LSTA1 (CEND-1) safe for humans?

CEND-1 has been tested in animals and humans, showing a favorable safety profile. It is quickly cleared from healthy tissues but remains in tumors, suggesting it is generally safe for human use. ^{1 6 7 8 9}

What makes the drug LSTA1 unique for treating pancreatic cancer?

LSTA1 (also known as iRGD) is unique because it helps drugs penetrate the dense tissue surrounding pancreatic tumors, which is a major barrier in treating this cancer. By targeting specific proteins on tumor cells, it enhances the delivery of therapeutic agents directly to the cancer cells, potentially improving treatment effectiveness. ^{3 4 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in people with metastatic pancreatic ductal adenocarcinoma. The main questions it aims to answer are: * is the new drug plus standard treatment safe and tolerable * is the new drug plus standard treatment more effective than standard treatment Participants will: * Visit the clinic three times every 28 days for treatment and tests * Have CT or MRI scans every 8 weeks while on treatment

Research Team

Kristen K. Buck, MD

Principal Investigator

Lisata Therapeutics, Inc.

Eligibility Criteria

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.

My cancer progressed after first-line FOLFIRINOX treatment.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Assessment of the Pharmacokinetics, Disposition, and Duration of Action of the Tumour-Targeting Peptide CEND-1. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A free cysteine prolongs the half-life of a homing peptide and improves its tumor-penetrating activity. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Perturbation of Autophagy by a Beclin 1-Targeting Stapled Peptide Induces Mitochondria Stress and Inhibits Proliferation of Pancreatic Cancer Cells. [2023]

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

iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer. [2022]

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

Enhanced Tumor Targeting and Penetration of Proteolysis-Targeting Chimeras through iRGD Peptide Conjugation: A Strategy for Precise Protein Degradation in Breast Cancer. [2023]

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

Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload. [2022]

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

New multifunctional molecular conjugate vector for targeting, imaging, and therapy of tumors. [2021]

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

Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor-Penetrating Peptides for Cancer Diagnosis and Treatment. [2020]

9. England pubmed.ncbi.nlm.nih.gov

In vivo noninvasive optical imaging of receptor-mediated RGD internalization using self-quenched Cy5-labeled RAFT-c(-RGDfK-)(4). [2016]

10. Germany pubmed.ncbi.nlm.nih.gov

Deep-Penetrating Triple-Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Histone methyltransferase G9a inhibitor-loaded redox-responsive nanoparticles for pancreatic ductal adenocarcinoma therapy. [2022]