Advanced Solid Tumors
Conditions
Keywords
Claudin 18.2, CLDN18.2
Brief summary
This is a Phase 1/2 open label study consisting of dose escalation cohorts (Phase 1) followed by expansion cohorts (Phase 2). The Phase 1 dose escalation population includes subjects with advanced solid tumors that are refractory to standard of care therapy or for whom no standard of care options are available. Once the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of single agent LCB02A is determined, the study will proceed to Phase 2 expansion cohorts in selected tumor types.
Interventions
DRUGLCB02A
CLDN18.2-directed human monoclonal antibody (Ab) linked to a topoisomerase I inhibiting payload.
Sponsors
LigaChem Biosciences, Inc.
AntibodyChem Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Phase 1 Dose Escalation: histologically or cytologically confirmed advanced solid tumors that are Claudin 18.2 positive and refractory to standard of care treatment. * Phase 2 Dose Expansion: selected histologically or cytologically confirmed advanced solid tumors that are Claudin 18.2 positive and refractory to standard of care treatment. Expansion cohort indications will be prioritized based on data from the Phase 1 dose escalation portion. * Prior treatment with Claudin 18.2 directed therapy is permitted. * Measurable disease as defined by RECIST v1.1 * Willingness to provide archival tumor tissue when available, or to undergo a pre-treatment biopsy if archival tissue is not available. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function as defined by: * Absolute neutrophil count ≥ 1.5 × 109/L , without colony stimulating factor support for the past 14 days * Platelet count ≥ 100 × 109/L * Hemoglobin level ≥ 9.0 g/dL * Total bilirubin ≤ 1.5× upper limit of normal (ULN) or \<3 x ULN with Gilbert's syndrome or liver metastases at baseline * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5× ULN (≤ 5.0× ULN for subjects with liver metastases) * Albumin ≥ 2.5 g/dL * Creatinine clearance ≥ 60 mL/min Key
Exclusion criteria
* Prior exposure to ADCs with a Topo1 inhibitor payload. * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients may be considered for enrollment if they have previously treated brain metastases that are clinically stable or radiologically stable for at least 14 days prior to the first dose. * Received radiotherapy within 21 days prior to the first dose of study drug. Note: For palliative radiotherapy for symptomatic improvement of non-central nervous system (CNS) lesions (total duration of radiotherapy ≤ 14 days), a radiation washout period of 7 days is required prior to the first dose. * Any medical conditions that may confound the study results, interfere with the patient's compliance, or impair the interests of the subject, as assessed by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of LCB02A (Phase 1 and 2) | Up to 48 months | Incidence and severity of AEs |
| Recommended Phase 2 dose of LCB02A (Phase 1) | Up to 24 months | Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics |
| Objective response rate (Phase 2) | Up to 24 months | Assessed by RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of LCB02A (Phase 1 and 2) | Up to 48 months | Pharmacokinetic parameters will be determined from observed concentrations of LCB02A |
| Duration of Response (Phase 1 and 2) | Up to 48 months | Assessed by RECIST v1.1 |
| Disease control rate (Phase 1 and Phase 2) | Up to 48 months | Assessed by RECIST v1.1 |
| Progression Free Survival (Phase 1 and Phase 2) | Up to 48 months | Assessed by RECIST v1.1 |
| Overall Survival (Phase 1 and Phase 2) | Up to 48 months | — |
Countries
Canada, South Korea, United States
Contacts
CONTACTDavid Browning
STUDY_DIRECTORRodrigo Ruiz Soto, M.D.
LigaChem Biosciences
Outcome results
None listed