LCB84 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumors

What is the Purpose of this Study?

This study focuses on individuals who have metastatic cancer (cancer that has spread) that has not responded to standard treatments or for whom no effective therapy is available. The purpose of the study is to evaluate LCB84, a type of drug called a TROP2 (human trophoblastic cell surface antigen 2) drug-antibody conjugate. LCB84 is an experimental medicine and works by using TROP2 as a target to deliver chemotherapy directly to tumor cells, unlike regular chemotherapy that goes everywhere in the body. The goal of the first part of the study is to find the highest tolerable dose of LCB84 when given alone and in combination with a immunotherapy drug called pembrolizumab. The second part of the study aims to determine the effectiveness of LCB84 alone or in combination with pembrolizumab in the treatment of various types of cancer.

Eligibility

* 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.

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.

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Where can I participate?

CS Cancer at Beverly Hills : Shannon Cyhan
CS Cancer at Cedars-Sinai Medical Center : Shannon Cyhan

More about this Clinical Trial

What is the full name of this clinical trial?

LCB84-1001: A First -In-Human Phase 1/2, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of TROP2-Directed Antibody-Drug Conjugate LCB84, as a Single Agent and in Combination with Pembrolizumab, in Patients with Advanced Solid Tumors

Study Details

Disease Type/Condition

Anus, Brain and Nervous System, Breast, Cervix, Colon, Esophagus

Principal Investigator

Yuan, Yuan

Co-Investigators

Alain Mita, Andrew Hendifar, Arsen Osipov, Bobbie Jo Rimel, David Hoffman, Edwin Posadas, Jeremy Lorber, Jin Sun Bitar, Jun Gong, Kamya Sankar, Karen Reckamp, Kevin Scher, Ronald Natale, Yuan Yuan

Age Group

Adult

Phase

I/II

IRB Number

STUDY00002944

ClinicalTrials.gov ID

NCT05941507

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Shannon Cyhan

Shannon.Cyhan@cshs.org