LSTA1 + Standard Care for Advanced Cancers

(BOLSTER Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, LSTA1, combined with standard treatment for cholangiocarcinoma, a type of bile duct cancer. The researchers aim to determine if this combination is safe and more effective than the standard treatment alone. Participants should have cholangiocarcinoma that is either newly diagnosed or has worsened after initial treatment. This trial is for those who have not recently undergone other major treatments and do not have serious infections or heart issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that LSTA1, when combined with standard treatments, may help treat advanced cancers. Previous studies combined LSTA1 with treatments like gemcitabine and nab-paclitaxel and found that LSTA1 is generally safe for patients. The most common side effects were mild, such as tiredness and nausea, while serious side effects were rare.

This trial is in an early stage, so information on safety might be limited. Early trials usually focus on ensuring treatments are safe and tolerable. So far, LSTA1 has been used safely in other cancer studies, providing some confidence in its safety. Prospective participants should discuss any concerns with the trial team before deciding to join. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for cholangiocarcinoma, such as chemotherapy and targeted therapy, LSTA1 is unique because it focuses on enhancing the body’s immune response to fight cancer. Researchers are excited about LSTA1 because it acts by modifying the tumor microenvironment, potentially making cancer cells more vulnerable to attack by the immune system. This innovative approach could lead to improved outcomes for patients, offering a new avenue of hope beyond the typical options.

What evidence suggests that LSTA1 plus standard care could be an effective treatment for cholangiocarcinoma?

This trial will compare the effects of adding LSTA1 to standard care for advanced bile duct cancer against placebo arms. Studies have shown that adding LSTA1 to the usual treatment may improve patient outcomes. Research suggests that early results are promising, with 60% of patients living at least two years. On average, patients remained disease-free for about 12 months. These early findings indicate that LSTA1 might be more effective than standard treatment alone for this type of cancer. ^{1 2 6 7 8}

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 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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05712356

A Study of LSTA1 When Added to Standard of Care Versus ... The study will include patients with previously untreated cholangiocarcinoma or those that have progressed after first-line treatment for cholangiocarcinoma.

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

Press Release Details The results also demonstrated promising early survival data, including a 60% two-year overall survival rate and a 12-month median disease-free ...

3. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT05712356

A Study of LSTA1 When Added to Standard of Care Versus ... A Study of LSTA1 When Added to Standard of Care Versus Standard of Care Alone in Patients With Advanced Solid Tumors. Print. Purpose. The goal ...

4. smartpatients.com smartpatients.com/trials/NCT05712356

A Study of LSTA1 When Added to Standard of Care Versus ... The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in patients with previously untreated ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-2-2023-bc412

LSTA1 + Standard Care for Advanced Cancers 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 ...

6. lisata.com lisata.com/bolster-clinical-trials/

BOLSTER: Cholangiocarcinoma Clinical Trial (Bile Duct ... The main goal of this clinical trial is to test the safety and therapeutic effect of a new drug plus standard treatment compared with standard treatment alone ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16290

A phase Ib/II, open-label, multicenter study to evaluate the ... Here we report the safety and efficacy results from a Phase Ib/II, multicenter study of LSTA1 plus (SoC) gemcitabine and locally produced nab-paclitaxel in ...

8. clinicaltrials.eu clinicaltrials.eu/inn/lsta1/

LSTA1: A Promising New Drug for Cancer Treatment LSTA1, also known as certepetide or CEND-1, is an investigational drug being studied for its potential to improve cancer treatment.