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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: LCB84
* Drug: Anti-PD-1 monoclonal antibody


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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