A Study to Investigate LYL797 in Adults With Solid Tumors

NCT ID: NCT05274451

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-29
• Study Completion Date: 2024-11-27

Brief Summary

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), non-small cell lung cancer (NSCLC), platinum-resistant epithelial ovarian cancer/ fallopian tube cancer/ primary peritoneal cancer (Ovarian cancer), or Endometrial cancer. The first part of the study will determine the safe dose for the next part of the study, and will enroll patients with TNBC, NSCLC, Ovarian or Endometrial cancer. The second part of the study will test that dose in additional patients with TNBC, NSCLC, Ovarian or Endometrial cancer.

Detailed Description

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

Conditions

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; Platinum-resistant Ovarian Cancer; Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Endometrial Cancer; Endometrioid Tumor; High Grade Serous Carcinoma; Ovarian Epithelial Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental LYL797

ROR1-targeted CAR T cells

Group Type: EXPERIMENTAL

LYL797

Intervention Type: BIOLOGICAL

LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy

Interventions

LYL797

LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years of age at time of informed consent
• Confirmation of ROR1 expression from a pretreatment tumor sample
• Histologically confirmed TNBC or NSCLC that is relapsed or refractory, metastatic or locally advanced and unresectable
• Platinum-resistant epithelial ovarian cancer/ fallopian tube cancer/ primary peritoneal cancer.
• Endometrial cancer.
• 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 other anti-ROR1 therapy
• Prior solid organ transplantation
• Active, untreated brain metastasis or leptomeningeal disease; however, stable, treated brain metastases are allowed
• Untreated or active infection at the time of screening or leukapheresis
• HIV-positive, HTLV-1-positive, active acute HAV, acute or chronic HBV or HCV, or active tuberculosis
• Impaired cardiac function or clinically significant cardiac disease
• Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequent), or lymphangitis carcinomatosis
• History of interstitial pneumonitis or pulmonary fibrosis.
• Systemic corticosteroids or other immunosuppressive medications within 14 days of leukapheresis
• Pregnant or lactating/nursing women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lyell Immunopharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jackie Walling, MBChB, PhD

Role: STUDY_DIRECTOR

Lyell Immunopharma, Inc.

Locations

Mayo Clinic

Scottsdale, Arizona, United States

University of California, Los Angeles

Santa Monica, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

Mayo Clinic

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

University of Chicago

Chicago, Illinois, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Oregon Health and Science University Hospital

Portland, Oregon, United States

Sidney Kimmel Cancer Center, Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute and Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

LYL797-101

Identifier Type: -

Identifier Source: org_study_id