Clinical trial NCT05941507: A Study to Evaluate TROP2 ADC LCB84 Single Agent and in Combination With an Anti-PD-1 Ab in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: TROP2
TROP-2
Breast Cancer
Head and Neck Cancer
TNBC
Gastric Cancer
Gastroesophageal
NSCLC
Lung Cancer
Glioblastoma
Endometrial Cancer
Ovarian Cancer
Cervical Cancer
Anal Cancer
Pancreatic Cancer
Urothelial Cancer
HNSCC
Salivary gland cancer
LCB84
Lead sponsor: LigaChem Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AntibodyChem Biosciences, Inc.
First posted: 2023-07-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, Phase 1/2 study to evaluate LCB84, a TROP2-directed antibody-drug conjugate, alone and in combination with an anti-PD-1 Ab, in dose escalation (Phase 1) followed by dose expansion (Phase 2).

The study population in dose escalation (Phase 1) consists of patients with advanced solid tumors refractory to standard of care, or for whom no standard of care exists. After the MTD and/or RP2D for single agent LCB84 is determined, dose escalation cohorts with select tumor types will be enrolled. Combination LCB84 and anti-PD-1 Ab will be evaluated in dose escalation after a minimum of 2 dose levels of single agent LCB84 have established DLT safety, to determine the MTD and/or RP2D of combination LCB84 and anti-PD-1 Ab, and to continue into dose expansion cohorts in select tumor types.


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).

Primary outcomes:
measure: Safety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2)
timeFrame: Up to 48 months
measure: Recommended Phase 2 Dose of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1)
timeFrame: Up to 24 months
measure: Objective Response Rate (Phase 2)
timeFrame: Up to 24 months
measure: Clinical Benefit Rate (Phase 2)
timeFrame: Up to 24 months
measure: Duration of Response (Phase 2)
timeFrame: Up to 24 months
measure: Time to Progression (Phase 2)
timeFrame: Up to 24 months
measure: Progression Free Survival (Phase 2)
timeFrame: Up to 24 months
measure: Overall Survival (Phase 2)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Plasma Concentrations of LCB84 (Phase 1 and 2)
timeFrame: Up to 48 months
measure: Evaluation of the immunogenicity of LCB84 (Phase 1 and 2)
timeFrame: Up to 48 months
measure: Objective Response Rate (Phase 1)
timeFrame: Up to 24 months
measure: Duration of Response (Phase 1)
timeFrame: Up to 24 months
measure: Time to Progression (Phase 1)
timeFrame: Up to 24 months
measure: Progression Free Survival (Phase 1)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: AntibodyChem Biosciences
name: Jennifer Wheler, MD
role: STUDY_DIRECTOR
References: