A Phase 1 Study of LNCB74 in Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Ovarian Cancer; Endometrial Cancer; Breast Cancer; Biliary Tract Cancer; Non-Small Cell Lung Cancer; Advanced or Metastatic Solid Tumors
• Interventions: Drug: LNCB74

• Registration Number: NCT06774963
• Lead Sponsor: NextCure, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-01-07
• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-13
• Study First Posted: 2025-01-14
• Status Verified: 2025-02
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-14
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 145

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2 - Dose Expansion / Optimization	LNCB74	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).
Part 1 - Dose Escalation and Backfills	LNCB74	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.

Primary Outcome Measures

Name	Time	Method
Evaluate the safety and tolerability of LNCB74	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
Define a recommended Phase 2 dose (RP2D) of LNCB74	Up to 24 months	Maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D) of LNCB74

Secondary Outcome Measures

Name	Time	Method
Characterize the immunogenicity of LNCB74	24 months	Incidence of anti-drug antibodies to LNCB74
Objective Response Rate (ORR)	24 months	Objective Response Rate (ORR) per RECIST v1.1
Duration of Response (DOR)	24 months	Duration of response per RECIST v1.1
Disease Control Rate (DCR)	24 months	Disease control rate per RECIST v1.1
Progression Free Survival Rate (PFSR)	6 months	Progression Free Survival Rate per RECIST v1.1
Correlate B7-H4 Expression with Objective Response Rate (ORR)	24 months	To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Objective Response Rate (ORR)
Correlate B7-H4 Expression with Duration of Response (DOR)	24 months	To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Duration of Response (DOR)
Correlate B7-H4 Expression with Disease Control Rate (DCR)	24 months	To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Disease Control Rate (DCR)
Correlate B7-H4 Expression with Progression Free Survival (PFS)	24 months	To determine B7-H4 expression by immunohistochemistry in a central lab and correlate B7-H4 expression with Progression Free Survival (PFS)
Progression Free Survival (PFS)	24 months	Progression Free Survival per RECIST v1.1
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	To evaluate the Time to Peak Drug Concentration (Tmax) of LNCB74
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	To evaluate the Area Under the Curve (AUC) of LNCB74
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	To evaluate the Half-life (T1/2) of LNCB74
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	To evaluate the Maximum Serum Concentration (Cmax) of LNCB74

Trial Locations

Locations (9)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University, Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Inova Schar Cancer Institute; 🇺🇸 Falls Church, Virginia, United States

John Theurer Cancer Ctr at Hackensack Univ. Med Ctr.; 🇺🇸 Hackensack, New Jersey, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

UT Health San Antonio - MD Anderson Cancer Center; 🇺🇸 San Antonio, Texas, United States