LNCB74 for Cancer

(LNCB74-01 Trial)

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NextCure, Inc.

Must not be taking: Immunotherapy, Steroids, Antibodies, Vaccines

Disqualifiers: CNS metastases, Pneumonitis, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

145 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LNCB74 for individuals with advanced solid tumors that cannot be surgically removed and have metastasized. The primary goal is to assess the safety and tolerability of LNCB74 and determine the optimal dose for future studies. Individuals with a confirmed diagnosis of advanced solid tumors who can provide a tumor sample may be suitable candidates for this trial. Participants will contribute to understanding how effectively LNCB74 targets tumors and ensure its safety for further testing. As a Phase 1 trial, this research aims to understand the treatment's effects in humans, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain cancer treatments or investigational agents within a specific time before starting the trial. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

Is there any evidence suggesting that LNCB74 is likely to be safe for humans?

Research has shown that LNCB74 has potential based on early lab tests. These studies demonstrate its strong ability to fight tumors, especially in lab models. LNCB74 is a unique treatment called an antibody-drug-conjugate, which combines an antibody with a drug to specifically target cancer cells. This method has proven safe for treating certain cancers that have a protein called B7-H4.

Compared to similar treatments being tested, LNCB74 has shown a better safety record in animal studies, suggesting it might be well-tolerated in humans too. However, since this is an early trial, the main goal is to determine its safety and optimal dosage. Participants in this study will help establish these factors, as the treatment is being tested in humans for the first time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often involve chemotherapy or radiation, LNCB74 is unique because it focuses on targeting a specific tumor type with a more refined approach. Researchers are excited about LNCB74 because it aims to identify the minimally safe and effective dose, potentially reducing side effects while maintaining anti-tumor activity. Additionally, by characterizing the pharmacodynamics in a homogenous population, this treatment could offer a more personalized and optimized therapy option for cancer patients, paving the way for better outcomes.

What evidence suggests that LNCB74 might be an effective treatment for cancer?

Research has shown that LNCB74 is a promising new treatment for advanced solid tumors. It targets a specific protein called B7-H4, found on some cancer cells. Early results indicate that LNCB74 effectively destroys cancer cells in the lab, particularly those from breast and ovarian cancers with this protein. Importantly, it causes minimal harm to cells lacking the protein. This suggests it might be both effective and safe for people with certain types of cancer. Participants in this trial will receive LNCB74 in different phases to determine the optimal dose and evaluate its safety and effectiveness. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including breast, ovarian, endometrial, biliary tract cancers, and non-small cell lung cancer. Participants must have a tumor that's progressed after treatment or has no satisfactory alternative treatment.

Inclusion Criteria

Participant provides written informed consent

My organs are working well.

Participant has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology

Exclusion Criteria

I have moderate to severe nerve damage affecting my senses or movement.

I had a bowel blockage within the last month.

Participant has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Doses of LNCB74 will be escalated to determine the maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D).

Up to 24 months

Multiple visits as per dosing schedule

Dose Expansion/Optimization

Evaluate safety, tolerability, anti-tumor activity, and pharmacodynamics of LNCB74 in a more homogenous population and determine recommended Phase 2 dose(s) (RP2D).

Up to 24 months

Multiple visits as per dosing schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• LNCB74

Trial Overview The study is testing LNCB74 in patients with various advanced solid tumors. It's an early-phase trial to find out the safest dose level and how well people can tolerate it.

How Is the Trial Designed?

Group I: Part 2 - Dose Expansion / Optimization Experimental Treatment 1 Intervention

Aim: The objectives of the Part 2 Dose Expansion/Optimization are: i) to evaluate safety, tolerability, anti-tumor activity, and pharmacodynamics of LNCB74 in a more homogenous population and ii) characterize the minimally safe and effective dose in a particular tumor type and determine recommended Phase 2 dose(s) (RP2D).

Group II: Part 1 - Dose Escalation and Backfills Experimental Treatment 1 Intervention

Aim: Doses of LNCB74 will be escalated to determine the maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D). One or more dose levels will be backfilled for safety and additional biomarker data.

Who Is Running the Clinical Trial?

NextCure, Inc.

Lead Sponsor

Trials

8

Recruited

660+

LigaChem Biosciences, Inc.

Industry Sponsor

Trials

14

Recruited

890+

Published Research Related to This Trial

Larotrectinib and entrectinib, first-generation TRK inhibitors, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with TRK gene fusions, showing rapid and long-lasting clinical benefits.

A safety analysis of 807 reports revealed that the most common adverse reactions were dizziness and pain, with no significant long-term safety concerns noted, indicating a favorable risk-benefit profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Liguori, V., Gaio, M., Zinzi, A., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

Neurocognitive adverse events (NAEs) are common in patients receiving lorlatinib, with 60% of patients in one cohort and 49% in another experiencing these effects, particularly cognitive and mood-related issues.

Factors such as brain metastases, brain radiation, psychiatric illness, and the use of certain medications (like antiepileptics and stimulants) are associated with an increased risk of developing NAEs, suggesting that patient history and treatment context are important for managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted Therapies. Dagogo-Jack, I., Abbattista, A., Murphy, JF., et al.[2023]

The study created a comprehensive cardiovascular toxicity knowledge base (tcTKB) that includes 14,351 drug-cardiovascular event pairs for 45 targeted cancer drugs, highlighting the potential for understanding cardiovascular risks associated with these treatments.

Analysis of the data revealed a positive correlation between cardiovascular events and both drug target genes and drug metabolism genes, suggesting that tcTKB could help researchers better understand the mechanisms behind cardiovascular toxicities linked to targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs. Xu, R., Wang, Q.[2022]

Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, demonstrates strong effectiveness in treating non-small cell lung cancer (NSCLC) patients with ALK mutations who have not responded to earlier treatments.

The safety profile of lorlatinib includes manageable side effects like hyperlipidemia and central nervous system issues, with few cases requiring permanent discontinuation, making it a well-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Management of Adverse Events Associated with Lorlatinib. Liao, D., Zhang, J., Yan, T., et al.[2023]

Citations

1. ir.nextcure.com ir.nextcure.com/static-files/fa8587d9-2a5a-4d0d-bee1-b31ee325b17a

LNCB74 is a potent and safe next-generation antibody- ... Representative data showing dose-dependent killing of B7-H4+ SKBR3 breast cancer cells by LNCB74 in vitro. Low toxicity to a B7-H4- knockout derivative, and.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3167

A phase 1 dose escalation and dose expansion study for ... LNCB74-01 is a phase 1, open-label, first-in-human study that will include dose escalation, safety, and biomarker backfills (Part 1) and randomized dose ...

3. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/NXTC-Q/pressreleases/35736850/nextcures-promising-phase-1-study-on-lncb74-a-potential-game-changer-in-cancer-treatment/

NextCure's Promising Phase 1 Study on LNCB74 ' The study aims to assess the safety, tolerability, and optimal dosing of LNCB74, a promising treatment for various advanced solid tumors, ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A1171

1051 LNCB74 is a B7-H4 targeting antibody-drug- ... Conclusions Together, these data show that LNCB74 is a potent and safe ADC for treating ovarian, breast and other B7-H4 positive cancer ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06774963

A Phase 1 Study of LNCB74 in Advanced Solid Tumors This is an open-label, phase 1, dose escalation and dose expansion study to determine safety and tolerability, and to determine the maximum tolerated dose.

6. ir.nextcure.com ir.nextcure.com/news-releases/news-release-details/nextcure-reports-preclinical-data-lncb74-and-additional-clinical

NextCure Reports Preclinical Data for LNCB74 and Additional ... LNCB74 demonstrates strong anti-tumor activity in multiple CDX and PDX tumor models. A single dose of 3 mg/kg resulted in durable tumor ...

7. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/1898/736330/Abstract-1898-LNCB74-is-a-potent-and-safe-next

Abstract 1898: LNCB74 is a potent and safe next-generation ... LNCB74 is a potent and safe next-generation antibody-drug-conjugate utilizing a cancer selective linker for the treatment of B7-H4 expressing cancers.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06774963

A Phase 1 Study of LNCB74 in Advanced Solid Tumors This is an open-label, phase 1, dose escalation and dose expansion study to determine safety and tolerability, and to determine the maximum tolerated dose ...