Evaluating LCB84 alone and with anti-PD-1 in advanced solid tumors

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of TROP2-Directed Antibody-Drug Conjugate LCB84, as a Single Agent and in Combination With an Anti-PD-1 Ab, in Patients With Advanced Solid Tumors

This study is testing a new treatment called LCB84, both alone and with another drug, to see if it can help people with advanced solid tumors that haven't responded to other therapies.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: LigaChem Biosciences, Inc. (industry)
• Drugs / interventions: prednisone
• Locations: 8 sites (Los Angeles, California and 7 other locations)
• Trial ID: NCT05941507 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and efficacy of LCB84, a TROP2-directed antibody-drug conjugate, both as a standalone treatment and in combination with an anti-PD-1 antibody for patients with advanced solid tumors that are resistant to standard therapies. The study is divided into two phases: Phase 1 focuses on dose escalation to determine the maximum tolerated dose (MTD) of LCB84, while Phase 2 will expand on selected tumor types based on Phase 1 results. Patients will undergo biopsies to evaluate treatment response and safety throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically or cytologically confirmed advanced solid tumors that are refractory to standard of care.

Not a fit: Patients with early-stage tumors or those who have not exhausted standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that currently have limited or no effective treatments.

How similar studies have performed: Other studies involving TROP2-directed therapies and immune checkpoint inhibitors have shown promise, suggesting potential for success in this approach.

Eligibility criteria

Key Inclusion Criteria:

* Phase 1 Dose Escalation: histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment.
* Phase 2 Dose Expansion\*: select histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment.

  \*expansion cohort indications to be prioritized based on data from Phase 1 dose escalation.
* Prior treatment with TROP2-directed therapy is permitted.
* Measurable disease as defined by RECIST v1.1 or RANO-BM.
* Willingness to provide archival tumor tissue when available or to undergo pre-treatment biopsy if not available.
* Mandatory pre- and on-treatment biopsies for enrichment cohorts in Phase 1 dose escalation and Phase 2 expansion cohorts if deemed medically feasible and safe.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function as defined by:

  * Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL), without colony-stimulating factor support for the past 14 days
  * Platelets ≥100.0 x 109/L (100 000/µL)
  * Hemoglobin ≥9.0 g/dL
  * Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤2.5 x ULN (AST, ALT ≤5 x ULN if liver metastases present)

Key Exclusion Criteria:

* Active or progressing central nervous system (CNS) metastases or any evidence of leptomeningeal disease.

Note: Patients with stable or treated CNS metastases may be eligible if all of the following criteria are met: 1) localized treatment for brain metastases completed at least 4 weeks prior to the first dose of study drug 2) no new or progressive neurologic symptoms and without need for immediate local therapy, steroids or anticonvulsants for symptom control (stable or decreasing steroid dose (a stable dose of ≤4 mg dexamethasone oral or equivalent) is permitted) 3) stable brain metastases for at least 1 month prior to screening (baseline) brain MRI.

* Persistent toxicities from previous systemic antineoplastic treatments \>Grade 1, excluding alopecia and vitiligo.
* Systemic antineoplastic therapy (including antiestrogen therapy) within 5 half-lives or 4 weeks, whichever is shorter, prior to first dose of the study drug.
* Concomitant use of systemic steroids at dose of \>10 mg of prednisone or its equivalent per day (exception for brain metastases, as described in exclusion criteria #1 above).

Where this trial is running

Los Angeles, California and 7 other locations

• Cedars Sinai Medical Center — Los Angeles, California, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• University of Michigan — Ann Arbor, Michigan, United States (RECRUITING)
• Tennessee Oncology — Nashville, Tennessee, United States (NOT_YET_RECRUITING)
• Mary Crowley Cancer Research — Dallas, Texas, United States (RECRUITING)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (NOT_YET_RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: David Browning

Conditions: Advanced Solid Tumors, TROP2, TROP-2, Breast Cancer, Head and Neck Cancer, TNBC, Gastric Cancer, Gastroesophageal