Advanced Solid Tumors
Conditions
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
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.
Interventions
DRUGLCB84
TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug
DRUGAnti-PD-1 monoclonal antibody
anti-PD-1 Ab
Sponsors
AntibodyChem Biosciences, Inc.
LigaChem Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Phase 2) | Up to 24 months | Survival rates |
| Recommended Phase 2 Dose of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (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, iRECIST, and RANO-BM |
| Clinical Benefit Rate (Phase 2) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Duration of Response (Phase 2) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Time to Progression (Phase 2) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Progression Free Survival (Phase 2) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Safety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2) | Up to 48 months | Incidence and severity of AEs and SAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Phase 1) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Duration of Response (Phase 1) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Time to Progression (Phase 1) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Progression Free Survival (Phase 1) | Up to 24 months | Assessed by RECIST 1.1, iRECIST, and RANO-BM |
| Plasma Concentrations of LCB84 (Phase 1 and 2) | Up to 48 months | Pharmacokinetic parameters will be determined from observed concentrations of LCB84 |
| Evaluation of the immunogenicity of LCB84 (Phase 1 and 2) | Up to 48 months | Occurrence of ADA measured in serum at selected timepoints during the study |
Countries
Canada, United States
Contacts
Primary ContactDavid Browning
Outcome results
None listed