LAT010 for Solid Tumors

(LIGHTSPEED-1 Trial)

Recruiting at 1 trial location

Overseen By Lightspeed Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Latticon Antibody Therapeutics, Inc

Must not be taking: Corticosteroids

Disqualifiers: Cardiovascular events, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot have used another systemic anti-cancer therapy within 3 weeks or 5 half-lives before the first dose of LAT010, whichever is shorter. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug LAT010 for solid tumors?

Research shows that LAT1, a component of LAT010, is linked to cancer growth and spread. Inhibiting LAT1 has been found to slow down cancer cell growth and reduce metastasis (spread of cancer) in various studies, suggesting it could be a promising target for cancer treatment. ^{1 2 3 4 5}

What makes the drug LAT010 unique for treating solid tumors?

LAT010 targets the L-type amino acid transporter 1 (LAT1), which is involved in tumor metabolism and proliferation, making it a novel approach compared to traditional treatments that may not specifically target this transporter. This mechanism could potentially inhibit tumor growth and metastasis by disrupting the cancer cells' nutrient supply. ^{1 4 6 7 8}

What is the purpose of this trial?

This is an open-label, multicenter, Phase 1/2, first-in-human (FIH), dose-escalation and cohort-expansion study of LAT010 to evaluate the safety, tolerability, immunogenicity, PK, PD, and antitumor activity in patients with advanced solid tumors. The study consists of 2 parts: Phase 1 dose-escalation and Phase 2 cohort expansion.

Research Team

John Li, PhD

Principal Investigator

Latticon Antibody Therapeutics, Inc

Eligibility Criteria

This trial is for patients with advanced solid tumors who have not responded to standard treatments. It's a first-in-human study, meaning it's the first time this treatment is being tested in people. Participants must be adults with measurable disease and acceptable organ function.

Inclusion Criteria

Expected life expectancy of >12 weeks per the Investigator.

There is a contraindication for the indicated standard therapies in the opinion of the Investigator.

Patients are willing and able to comply with the protocol-related procedures (including screening evaluations), such as visits, treatment plans, laboratory assessments, and other requirements of the study.

Exclusion Criteria

Other exclusions:

Recent medical concerns exclusions:

I am willing and able to follow the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

LAT010 monotherapy with ascending doses in patients with locally advanced or metastatic solid tumors. LAT010 will be administered in planned 7 dose cohorts to determine safety and RP2D.

4 weeks per cycle

Weekly visits for IV injection

Phase 2 Cohort Expansion

LAT010 monotherapy at the RP2D and in combination with a PD-1 inhibitor in patients with selected tumor types. Antitumor activity and safety will be further evaluated.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 months

Treatment Details

Interventions

• LAT010

Trial Overview The trial is testing LAT010 alone and in combination with an immune checkpoint inhibitor (ICI) to see how safe they are and how well they work against tumors. The study has two parts: early testing of different doses (Phase 1) followed by expansion to more patients at selected dose levels (Phase 2).

Participant Groups

Group I: Phase 2 LAT010 Dose Expansion Experimental Treatment 2 Interventions

LAT010 monotherapy at the RP2D and in combination with a PD-1 inhibitor in patients with selected tumor types. LAT010 will be administered at multiple dose levels based on the results of Phase 1. Antitumor activity and safety will be further evaluated.

Group II: Phase 1 LAT010 Dose Escalation Experimental Treatment 1 Intervention

LAT010 monotherapy with ascending doses in patients with locally advanced or metastatic solid tumors. LAT010 will be administered in planned 7 dose cohorts to determine safety and RP2D. PD profile of LAT010 will also be characterized.

Who Is Running the Clinical Trial?

Latticon Antibody Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

150+

Findings from Research

In a study of 93 cancer patients, LAT1 and CD98 expressions were significantly higher in metastatic tumors compared to primary tumors, suggesting their role in cancer metastasis.

LAT1 expression was closely linked to increased cell proliferation and angiogenesis, indicating that targeting LAT1 could be a potential strategy in managing metastatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms. Kaira, K., Oriuchi, N., Imai, H., et al.[2017]

LAT1 was found to be overexpressed in various subtypes of HER2 negative breast cancer, indicating its potential as a prognostic marker and a target for therapy, especially since it was present in 83.6% of HER2 negative cases.

Although LAT1 expression did not show significant survival differences in HER2 negative patients, there was a concerning trend where 5 out of 55 patients with LAT1 positive expression died, compared to none in the LAT1 negative group, suggesting a possible link between LAT1 and poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LAT1 (SLC7A5) Overexpression in Negative Her2 Group of Breast Cancer: A Potential Therapy Target. Bodoor, K., Almomani, R., Alqudah, M., et al.[2021]

Inhibition of L-type amino acid transporter 1 (LAT1) using the selective inhibitor nanvuranlat significantly reduced cancer cell proliferation, migration, and invasion in B16-F10 melanoma mouse models, indicating its potential as a target for anti-metastasis therapy.

The study found that LAT1 inhibition downregulated the mTOR signaling pathway and decreased the expression of integrin αvβ3, which is linked to reduced metastasis in various organs, including the lungs and lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models. Shi, Z., Kaneda-Nakashima, K., Ohgaki, R., et al.[2023]

In a study of 250 breast cancer patients, high expression of the L-type amino acid transporter 1 (LAT1) was linked to more aggressive tumor characteristics and poorer patient outcomes, particularly in ER-positive and HER2-negative cases.

LAT1 expression may serve as a potential therapeutic target in breast cancer, especially for patients with luminal B-like tumors, as it is associated with increased tumor immunoreaction and a higher risk of poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer. Kurozumi, S., Kaira, K., Matsumoto, H., et al.[2022]

LAT1 is overexpressed in all types of Non-Hodgkin lymphoma (NHL) and its expression level correlates with lymphoma grade, indicating that higher LAT1 levels are associated with more aggressive forms of the disease.

Inhibiting LAT1 with the specific inhibitor JPH203 effectively reduces lymphoma cell growth, suggesting that targeting LAT1 could be a promising new treatment strategy for NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma. Jigjidkhorloo, N., Kanekura, K., Matsubayashi, J., et al.[2022]

LAT1 is significantly overexpressed in human epithelial ovarian cancers, suggesting it plays a crucial role in the growth and spread of these tumors, as shown in a study of 63 surgical specimens.

Inhibiting LAT1 with BCH effectively reduced the proliferation and migration of ovarian cancer cells (OVCAR-3) and blocked their uptake of l-leucine, indicating that targeting LAT1 could be a promising strategy for developing new cancer therapies that spare normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. Kaji, M., Kabir-Salmani, M., Anzai, N., et al.[2018]

In a study of 134 patients with bile duct adenocarcinomas, high expression of the L-type amino acid transporter LAT1 was found to be a significant indicator of poor prognosis, suggesting its potential as a prognostic marker.

LAT1 expression, along with surgical margin and pT stage, were identified as independent prognostic factors, indicating that targeting LAT1 could be a promising strategy for new cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas. Yanagisawa, N., Hana, K., Nakada, N., et al.[2021]

The LAT1-specific inhibitor JPH203 shows promise in reducing tumor size and metastasis in colorectal cancer (CRC) by targeting LAT1, which is predominantly expressed in cancerous tissues and associated with tumor progression.

In both in vitro and in vivo studies, JPH203 effectively inhibited tumor growth and affected pathways related to amino acid metabolism and stromal activation, suggesting its potential as a therapeutic agent for CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis. Otani, R., Takigawa, H., Yuge, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms. [2017]

2. Thailand pubmed.ncbi.nlm.nih.gov

LAT1 (SLC7A5) Overexpression in Negative Her2 Group of Breast Cancer: A Potential Therapy Target. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer. [2022]

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

Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Properties of L-type amino acid transporter 1 in epidermal ovarian cancer. [2018]

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

High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis. [2023]