LNCB74 for Cancer

(LNCB74-01 Trial)

Recruiting at3 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: NextCure, Inc.

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

Disqualifiers: CNS metastases, Pneumonitis, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 and / or recommended phase 2 dose of LNCB74 in participants with advanced solid tumors.

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.

What safety data exists for LNCB74 or similar treatments?

The safety profiles of similar targeted cancer drugs show that they can cause adverse reactions like dizziness and pain, but no major long-term safety concerns have been identified. However, these drugs can increase the risk of serious and fatal adverse events, so continuous safety monitoring is important. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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

I am 18 years old or older.

I am not pregnant, breastfeeding, or able to have children.

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

Trial Timeline

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

Treatment Details

Interventions

• LNCB74 (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Switzerland 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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Recent Advances in the Management of Adverse Events Associated with Lorlatinib. [2023]

3. India 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. [2020]

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

Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted Therapies. [2023]

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

tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs. [2022]