A Study to Evaluate TROP2 ADC LCB84 Single Agent and in Combination With an Anti-PD-1 Ab in Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05941507
• Other study ID #: LCB84-1001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 5, 2023
• Est. completion date: May 2027

Study information

• Verified date: April 2024
• Source: LigaChem Biosciences, Inc.
• Contact: David Browning
• Phone: +1-615-975-7776
• Email: dbrowning[@]ligachembio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• LCB84
TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug
• Anti-PD-1 monoclonal antibody
anti-PD-1 Ab

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	University of Michigan	Ann Arbor	Michigan
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
LigaChem Biosciences, Inc.	AntibodyChem Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2)	Incidence and severity of AEs and SAEs	Up to 48 months
Primary	Recommended Phase 2 Dose of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1)	Based on tolerability, preliminary anti tumor activity, and pharmacokinetics	Up to 24 months
Primary	Objective Response Rate (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Primary	Clinical Benefit Rate (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Primary	Duration of Response (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Primary	Time to Progression (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Primary	Progression Free Survival (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Primary	Overall Survival (Phase 2)	Survival rates	Up to 24 months
Secondary	Plasma Concentrations of LCB84 (Phase 1 and 2)	Pharmacokinetic parameters will be determined from observed concentrations of LCB84	Up to 48 months
Secondary	Evaluation of the immunogenicity of LCB84 (Phase 1 and 2)	Occurrence of ADA measured in serum at selected timepoints during the study	Up to 48 months
Secondary	Objective Response Rate (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Secondary	Duration of Response (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Secondary	Time to Progression (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Secondary	Progression Free Survival (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months