LSTA1 + Standard Care for Advanced Cancers

(BOLSTER Trial)

Recruiting at 26 trial locations

Overseen By Kathryn Shantz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lisata Therapeutics, Inc.

Disqualifiers: Active infection, Hepatitis, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, based on individual response

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called LSTA1 combined with standard treatment in patients with advanced cholangiocarcinoma. It aims to find out if this combination is safer and more effective than the standard treatment alone.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug LSTA1 (CEND-1) for advanced cancers?

Research shows that CEND-1 helps other cancer drugs work better by making it easier for them to reach and stay in tumors. In studies with animals and patients, CEND-1 was found to stay in tumors longer than in healthy tissues, suggesting it could improve the effectiveness of cancer treatments. ^{1 2 3 4 5}

Is LSTA1 (CEND-1) safe for human use?

CEND-1 has been studied in both animals and humans, showing a favorable safety profile. In patients with metastatic pancreatic cancer, it was cleared from most healthy tissues within a few hours, suggesting it is generally safe for human use. ^{1 2 4 6 7}

What makes the drug LSTA1 unique for treating advanced cancers?

LSTA1 (CEND-1) is unique because it is a tumor-targeting peptide that enhances the delivery of other anti-cancer drugs directly into tumors, improving their effectiveness. It works by penetrating the tumor environment and has a prolonged effect, allowing for better drug accumulation in tumors compared to traditional treatments. ^{1 2 4 8 9}

Research Team

Kristen K Buck, MD

Principal Investigator

Lisata Therapeutics, Inc.

Eligibility Criteria

This trial is for adults with advanced head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, or cholangiocarcinoma. They must have progressed after first-line therapy, be expected to live at least 3 months, have good organ function and performance status. Exclusions include recent major surgery or radiation, active infections including hepatitis B/C or HIV, certain autoimmune diseases, other cancers treated within the last 3 years, significant heart disease within the past 6 months.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer is in my head or neck, has returned or spread, and didn't respond to initial immunotherapy.

Life expectancy ≥ 3 months

Exclusion Criteria

I haven't had active treatment for another cancer in the last 3 years, except for certain curable types.

I am allergic to taxanes or their pre-treatments for head and neck cancer.

I do not have active tuberculosis.

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 full treatment regimen, with tumor scans every 8 weeks

Variable, based on individual response

End-of-Treatment Follow-up

Participants have an end-of-treatment follow-up 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 tests a new drug called LSTA1 added to standard cancer treatments (like Gemcitabine and Cisplatin) versus just the standard treatments alone. It aims to find out if adding LSTA1 is safe and improves outcomes compared to standard care in patients with specific types of advanced solid tumors.

Participant Groups

Group I: LSTA1 arm for Untreated Cholangiocarcinoma Experimental Treatment 4 Interventions

Group II: LSTA1 arm for Second-Line Cholangiocarcinoma Experimental Treatment 2 Interventions

Group III: Placebo arm for Second-Line Cholangiocarcinoma Placebo Group 2 Interventions

Group IV: Placebo arm for Untreated Cholangiocarcinoma Placebo Group 4 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 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]

Two peptides, PKRGFQD and SNTRVAP, were identified as effective in targeting androgen-independent prostate cancer cells, showing potential for use in targeted therapies.

The study discovered that the peptides bind to specific receptors, α-2-macroglobulin and GRP78, which are active in this type of cancer, suggesting new avenues for drug development against metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors. Mandelin, J., Cardó-Vila, M., Driessen, WH., et al.[2021]

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 truncated form of the tumor-homing peptide LyP-1, known as tLyP-1, enhances drug delivery by effectively penetrating solid tumors and facilitating the internalization of therapeutic agents through the neuropilin-1 and neuropilin-2 pathways.

tLyP-1 demonstrates superior tumor-targeting capabilities compared to its parent peptide, leading to improved extravasation of nanoparticles into tumor tissue, making it a promising candidate for targeted therapies in breast cancer and potentially other tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transtumoral targeting enabled by a novel neuropilin-binding peptide. Roth, L., Agemy, L., Kotamraju, VR., et al.[2012]

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-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]

The study developed a dual-channel fluorescent cyclic iRGD peptide that allows for tracking of both the N- and C-terminal fragments during tumor internalization, revealing that they co-internalize into cancer cells and localize in endosomal-lysosomal compartments.

The new theranostic peptide platform, Cy5.5-iRGDC-Pt(IV), demonstrated superior tumor imaging and induced tumor-specific apoptosis with negligible systemic toxicity, suggesting its potential for effective cancer-targeted therapy and imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theranostic iRGD peptide containing cisplatin prodrug: Dual-cargo tumor penetration for improved imaging and therapy. Cho, HJ., Park, SJ., Lee, YS., et al.[2020]

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

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

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

Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors. [2021]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Transtumoral targeting enabled by a novel neuropilin-binding peptide. [2012]

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

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

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Theranostic iRGD peptide containing cisplatin prodrug: Dual-cargo tumor penetration for improved imaging and therapy. [2020]