A Phase 1 Study of LNCB74 in Advanced Solid Tumors (LNCB74-01)

December 8, 2025 updated by: NextCure, Inc.

A Phase 1, Open-label, Dose Escalation and Dose Expansion Study for LNCB74, a B7-H4 Targeted Antibody Drug Conjugate, as Monotherapy in Participants With 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 and / or recommended phase 2 dose of LNCB74 in participants with advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

145

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Family Cancer Institute
        • Principal Investigator:
          • Monica Mita, MD
        • Contact:
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Recruiting
        • St. Elizabeth Healthcare
        • Principal Investigator:
          • Daniel Flora, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
        • Principal Investigator:
          • Joyce Liu, MD
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University, Siteman Cancer Center
        • Contact:
        • Principal Investigator:
          • Dan Morgansztern, MD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Not yet recruiting
        • John Theurer Cancer Ctr at Hackensack Univ. Med Ctr.
        • Principal Investigator:
          • Martin Gutierrez
        • Contact:
    • New York
      • Buffalo, New York, United States, 14203
        • Recruiting
        • Roswell Park Comprehensive Cancer Center
        • Principal Investigator:
          • Emese Zsiros, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Taussig Cancer Institute
        • Principal Investigator:
          • Wen Wee Ma, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Comprehensive Center at Jefferson
        • Principal Investigator:
          • Ida Micaily, MD
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • UPMC
        • Contact:
        • Principal Investigator:
          • Julia Foldi, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson
        • Principal Investigator:
          • Siqing Fu, MD
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Completed
        • NEXT Oncology
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • UT Health San Antonio - MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Daruka Mahadevan
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • Recruiting
        • Intermountain/LDS Hospital Ph 1 Research Program
        • Contact:
        • Principal Investigator:
          • Caroline Nebhan
    • Virginia
      • Falls Church, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Principal Investigator:
          • Raymond Wadlow, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The participant provides written informed consent
  2. ≥ 18 years of age on day of signing informed consent.
  3. Participant with histologically or cytologically confirmed diagnosis of advanced unresectable and/or metastatic solid tumors
  4. A male participant must agree to use contraception and refrain from sperm donation or expecting to father a child
  5. A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential
  6. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
  7. Able to provide tumor tissue sample.
  8. Willing to undergo fresh tumor biopsy at Screening and On-treatment if archival tissue not available
  9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  10. Life expectancy greater than or equal to 12 weeks as judged by the Investigator.
  11. Have adequate organ function

Exclusion Criteria:

  1. A WOCBP who has a positive serum pregnancy test (within 72 hours) prior to treatment.
  2. Has received prior investigational agents within 4 weeks prior to treatment.
  3. Has received anti-cancer chemotherapy (Immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy within 2 weeks prior to treatment.
  4. Has received antibody-based anti-cancer therapy within 4 weeks prior to treatment.
  5. Has received targeted agents and small molecules within 2 weeks or 5 half-lives, whichever is longer.
  6. Has received prior platinum-based chemotherapy and progressed within 4 weeks of initiating therapy (platinum-refractory disease)
  7. Has received an ADC with MMAE payload.
  8. Has received prior radiotherapy within 2 weeks of start of study treatment for focal radiation or within 4 weeks for wide-field radiotherapy
  9. Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
  10. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
  11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
  12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  13. Has known active CNS metastases and/or carcinomatous meningitis
  14. Has severe hypersensitivity (≥ Grade 3), known allergy or reaction LNCB74 or any of its excipients.
  15. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
  16. Has active ≥Grade 2 sensory or motor neuropathy.
  17. Has active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy or any clinically significant corneal disease.
  18. Has an active infection requiring systemic therapy.
  19. Any major surgery within 4 weeks of study drug administration.
  20. Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
  21. Prior organ or tissue allograft.
  22. Uncontrolled or significant cardiovascular disease
  23. Participants with serious or uncontrolled medical disorders.
  24. Participants who are on total parenteral nutrition (TPN)
  25. Participants with history of bowel obstruction within one month of screening
  26. Participants with history of significant ascites requiring paracentesis within 2 weeks of screening
  27. Has a known history of human immunodeficiency virus (HIV) infection with an acquired immune deficiency syndrome (AIDS)-defining opportunistic infection within the last year, or a current CD4 count <350 cells/µl
  28. Has known active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
  29. 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
  30. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 - Dose Escalation and Backfills
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.
Drug: LNCB74
LNCB74 is an antibody drug conjugate being evaluated as a potential treatment for participants with advanced solid tumors. Participants will receive LNCB74 into the vein (IV; intravenously) in 21-day dosing cycles. Participants will continue treatment in the absence of unacceptable toxicities and unequivocal disease progression.
Experimental: Part 2 - Dose Expansion / Optimization
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).
Drug: LNCB74
LNCB74 is an antibody drug conjugate being evaluated as a potential treatment for participants with advanced solid tumors. Participants will receive LNCB74 into the vein (IV; intravenously) in 21-day dosing cycles. Participants will continue treatment in the absence of unacceptable toxicities and unequivocal disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety and tolerability of LNCB74
Time Frame: 24 months
Incidence of AEs, SAEs, AEs meeting protocol defined DLT criteria, AEs leading to discontinuation and death, and laboratory abnormalities per NCI CTCAE v5.0
24 months
Define a recommended Phase 2 dose (RP2D) of LNCB74
Time Frame: Up to 24 months
Maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D) of LNCB74
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize the immunogenicity of LNCB74
Time Frame: 24 months
Incidence of anti-drug antibodies to LNCB74
24 months
Objective Response Rate (ORR)
Time Frame: 24 months
Objective Response Rate (ORR) per RECIST v1.1
24 months
Duration of Response (DOR)
Time Frame: 24 months
Duration of response per RECIST v1.1
24 months
Disease Control Rate (DCR)
Time Frame: 24 months
Disease control rate per RECIST v1.1
24 months
Progression Free Survival Rate (PFSR)
Time Frame: 6 months
Progression Free Survival Rate per RECIST v1.1
6 months
Correlate B7-H4 Expression with Objective Response Rate (ORR)
Time Frame: 24 months
To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Objective Response Rate (ORR)
24 months
Correlate B7-H4 Expression with Duration of Response (DOR)
Time Frame: 24 months
To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Duration of Response (DOR)
24 months
Correlate B7-H4 Expression with Disease Control Rate (DCR)
Time Frame: 24 months
To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Disease Control Rate (DCR)
24 months
Correlate B7-H4 Expression with Progression Free Survival (PFS)
Time Frame: 24 months
To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Progression Free Survival (PFS)
24 months
Progression Free Survival (PFS)
Time Frame: 24 months
Progression Free Survival per RECIST v1.1
24 months
Time to Peak Drug Concentration (Tmax) of LNCB74
Time Frame: Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
To evaluate the Time to Peak Drug Concentration (Tmax) of LNCB74
Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
Area Under the Curve (AUC) of LNCB74
Time Frame: Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
To evaluate the Area Under the Curve (AUC) of LNCB74
Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
Half-life (T1/2) of LNCB74
Time Frame: Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
To evaluate the Half-life (T1/2) of LNCB74
Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
Maximum Serum Concentration (Cmax) of LNCB74
Time Frame: Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9
To evaluate the Maximum Serum Concentration (Cmax) of LNCB74
Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NextCure, Inc.

Collaborators

LigaChem Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

January 8, 2025

First Submitted That Met QC Criteria

January 13, 2025

First Posted (Actual)

January 14, 2025

Study Record Updates

Last Update Posted (Actual)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 8, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LNCB74-01
  • 168703 (Other Identifier: NextCure, Inc.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe