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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: LCB84; Drug: Anti-PD-1 monoclonal antibody

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: David Browning; Phone Number: +1-615-975-7776; Email: dbrowning@ligachembio.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Principal Investigator: Philippe Bedard, MD
      • Contact: Study Coordinator; Phone Number: 416 946 4501 x 4737; Email: virtuoso@uhn.ca
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
      • Principal Investigator: Yuan Yuan, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Glenn Hanna, MD
      • Contact: DFCI External Referral; Email: dfcicctiexternalreferral@dfci.harvard.edu
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Paul Swiecicki, MD
      • Contact: Cancer Answer Line; Phone Number: 800-865-1125; Email: CancerAnswerLine@med.umich.edu
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
      • Contact: Douglas Orr, MD; Phone Number: 972-566-3000; Email: dorr@marycrowley.org
      • Principal Investigator: Douglas Orr, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Funda Meric-Bernstam, MD
      • Contact: Anjali Raina; Phone Number: 713-792-3238; Email: ARaina@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCB84 monotherapy; IV infusion Q3W	Drug: LCB84; TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug
Experimental: LCB84 + anti-PD-1; IV infusion Q3W	Drug: LCB84; TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug; Drug: Anti-PD-1 monoclonal antibody; anti-PD-1 Ab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Objective Response Rate (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Clinical Benefit Rate (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Duration of Response (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Time to Progression (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Progression Free Survival (Phase 2)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Overall Survival (Phase 2)	Survival rates	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of LCB84 (Phase 1 and 2)	Pharmacokinetic parameters will be determined from observed concentrations of LCB84	Up to 48 months
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
Objective Response Rate (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Duration of Response (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Time to Progression (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months
Progression Free Survival (Phase 1)	Assessed by RECIST 1.1, iRECIST, and RANO-BM	Up to 24 months

Collaborators and Investigators

• Sponsor: LigaChem Biosciences, Inc.
• Collaborators: AntibodyChem Biosciences, Inc.
• Investigators: Study Director: Jennifer Wheler, MD, AntibodyChem Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 4, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Head and Neck Cancer; Lung Cancer; NSCLC; Gastric Cancer; Pancreatic Cancer; Cervical Cancer; Ovarian Cancer; TNBC; HNSCC; Glioblastoma; Endometrial Cancer; Urothelial Cancer; TROP2; Gastroesophageal; Anal Cancer; Salivary gland cancer; TROP-2; LCB84
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: LCB84-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No