A Phase 1 Study of LNCB74 in Advanced Solid Tumors

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Evaluate the safety and tolerability of LNCB74 [Time frame: 24 months]
• Define a recommended Phase 2 dose (RP2D) of LNCB74 [Time frame: Up to 24 months]

Secondary outcome measures (12)

• Characterize the immunogenicity of LNCB74 [Time frame: 24 months]
• Objective Response Rate (ORR) [Time frame: 24 months]
• Duration of Response (DOR) [Time frame: 24 months]
• Disease Control Rate (DCR) [Time frame: 24 months]
• Progression Free Survival Rate (PFSR) [Time frame: 6 months]
• Correlate B7-H4 Expression with Objective Response Rate (ORR) [Time frame: 24 months]
• Correlate B7-H4 Expression with Duration of Response (DOR) [Time frame: 24 months]
• Correlate B7-H4 Expression with Disease Control Rate (DCR) [Time frame: 24 months]
• Correlate B7-H4 Expression with Progression Free Survival (PFS) [Time frame: 24 months]
• Progression Free Survival (PFS) [Time frame: 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]
• 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]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• A WOCBP who has a positive serum pregnancy test (within 72 hours) prior to treatment.
• Has received prior investigational agents within 4 weeks prior to treatment.
• Has received anti-cancer chemotherapy (Immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy within 2 weeks prior to treatment.
• Has received antibody-based anti-cancer therapy within 4 weeks prior to treatment.
• Has received targeted agents and small molecules within 2 weeks or 5 half-lives, whichever is longer.
• Has received prior platinum-based chemotherapy and progressed within 4 weeks of initiating therapy (platinum-refractory disease)
• Has received an ADC with MMAE payload.
• Has received prior radiotherapy within 2 weeks of start of study treatment for focal radiation or within 4 weeks for wide-field radiotherapy
• Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• 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
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active CNS metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥ Grade 3), known allergy or reaction LNCB74 or any of its excipients.
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
• Has active ≥Grade 2 sensory or motor neuropathy.
• Has active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy or any clinically significant corneal disease.
• Has an active infection requiring systemic therapy.
• Any major surgery within 4 weeks of study drug administration.
• 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.
• Prior organ or tissue allograft.
• Uncontrolled or significant cardiovascular disease
• Participants with serious or uncontrolled medical disorders.
• Participants who are on total parenteral nutrition (TPN)
• Participants with history of bowel obstruction within one month of screening
• Participants with history of significant ascites requiring paracentesis within 2 weeks of screening
• 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
• Has known active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection
• 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
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• Hoag Family Cancer Institute — Newport Beach
• St. Elizabeth Healthcare — Edgewood
• Dana Farber Cancer Institute — Boston
• Washington University, Siteman Cancer Center — St Louis
• John Theurer Cancer Ctr at Hackensack Univ. Med Ctr. — Hackensack
• Roswell Park Comprehensive Cancer Center — Buffalo
• Cleveland Clinic Taussig Cancer Institute — Cleveland
• Sidney Kimmel Comprehensive Center at Jefferson — Philadelphia
• … and 6 more centers

Identifiers

NCT: NCT06774963 · LNCB74-01 · 168703

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗