A Study to Investigate LYL797 in Adults With Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ relapsed or refractory triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). The first part of the study will determine the safe dose for the next part of the study, and will enroll TNBC and NSCLC patients. The second part of the study will test that dose in additional TNBC and NSCLC patients.

Detailed Description
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This Phase 1, single-arm, open-label, multi-center, dose-escalation and -expansion study will evaluate the safety and tolerability of LYL797, ROR1-targeting CAR T cells, in adults with relapsed and/or refractory ROR1+ triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). The dose-escalation phase includes TNBC and NSCLC patients, and will investigate 4 dose levels to determine the recommended Phase 2 dose (RP2D). The dose-expansion phase will enroll both TNBC and NSCLC patients at the RP2D.

Official Title
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A Phase 1 Study to Assess the Safety and Efficacy of LYL797, ROR1-Targeting CAR T Cells, in Adults With Relapsed and/or Refractory Solid-Tumor Malignancies

Conditions
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Triple Negative Breast Cancer, TNBC - Triple-Negative Breast Cancer, Non-small Cell Lung Cancer, Non Small Cell Lung Cancer, Non Small Cell Lung Cancer Metastatic, Non-Small Cell Carcinoma of Lung, TNM Stage 4, Advanced Breast Cancer, Advanced Lung Carcinoma, NSCLC, NSCLC, Recurrent, NSCLC Stage IV, Relapsed Cancer, Relapse/Recurrence, Recurrent Breast Cancer, Recurrent NSCLC

Intervention / Treatment
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* Biological: LYL797


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age at time of informed consent Histologically confirmed TNBC or NSCLC that is relapsed or refractory, metastatic or locally advanced and unresectable that is ROR1+ by central laboratory immunohistochemistry (IHC) Measurable disease including a target lesion and an additional lesion for biopsy Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate organ and marrow function Women of childbearing potential must have a negative pregnancy test at screening All participants must agree to practice highly effective methods of contraception Exclusion Criteria: Prior treatment with any adoptive T-cell therapy or anti-ROR1 therapy Prior solid organ transplantation Active, untreated brain metastasis or leptomeningeal disease; stable, treated brain involvement by disease is allowed Untreated or active infection at the time of screening or leukapheresis HIV-positive, HTLV-1-positive, active acute or chronic HBV or HCV, or active tuberculosis Impaired cardiac function or clinically significant cardiac disease Uncontrolled pleural or pericardial effusion Systemic corticosteroids or other immunosuppressive medications within 14 days of leukapheresis Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors Pregnant or lactating/nursing women

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
Intervention Model: Single Group Assignment
Interventional Model Description: Single-arm, open-label, dose-escalation and -expansion study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental LYL797<br>ROR1-targeted CAR T cells | Biological: LYL797<br>* LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate incidence of dose-limiting toxicities (DLTs) | Incidence of dose-limiting toxicities (DLTs) | Up to 2 years | 
| Evaluate incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years | 
| Evaluate severity of treatment-emergent adverse events (TEAEs) | Severity of treatment-emergent adverse events (TEAEs) | Up to 2 years | 
| Determine recommended Phase 2 Dose (RP2D) | Dose-escalation phase to determine the recommended Phase 2 dose | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1 | Overall response rate (ORR) by RECIST, version 1.1 | Up to 2 years | 
| Evaluate anti-tumor activity of LYL797 based on complete response (CR) rate by RECIST, version 1.1 | Complete response (CR) rate by RECIST, version 1.1 | Up to 2 years | 
| Evaluate duration of response (DOR) | Duration of response (DOR) | Up to 2 years | 
| Evaluate progression-free survival (PFS) | Progression-free survival (PFS) | Up to 2 years | 
| Evaluate overall survival (OS) | Overall survival (OS) | Up to 2 years | 
| Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples | Maximum concentration of LYL797 (Cmax) | Up to 2 years | 
| Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples | Time to Cmax (Tmax) | Up to 2 years | 
| Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB) | Area under the concentration-time curve (AUC) | Up to 2 years | 
| Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples | Persistence of LYL797 in PB | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T-cell therapy, CAR T, CAR T-cell, CAR-T, CAR-T cell therapy, CAR-T cell, ROR1, ROR1+, ROR1 positive, cell therapy, immunotherapy, relapsed, refractory, solid tumor, advanced, metastatic, breast cancer, lung cancer, triple negative breast cancer, non small cell lung cancer