A Study to Investigate LYL797 in Adults With Solid Tumors

NCT05274451 | Terminated Phase 1 FDA Drug

• 1 other identifier: LYL797-101
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 18

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.

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

Keywords

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; ovarian cancer; endometrial cancer

Outcome Measures

Primary Outcomes (4)

• Evaluate incidence of dose-limiting toxicities (DLTs)

  Incidence of dose-limiting toxicities (DLTs)

  Up to 28 days

• 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 Outcomes (8)

• Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1

  Up to 2 years

• Evaluate duration of response (DOR)

  Up to 2 years

• Evaluate progression-free survival (PFS)

  Up to 2 years

• Evaluate overall survival (OS)

  Up to 2 years

• Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples

  Up to 2 years

Study Arms (1)

Experimental LYL797

EXPERIMENTAL

ROR1-targeted CAR T cells

Biological: LYL797

Interventions

LYL797 BIOLOGICAL

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

Experimental LYL797

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lyell Immunopharma, Inc.: lead

Study Sites (18)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of California, Los Angeles

Santa Monica, California, 90404, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University Hospital

Portland, Oregon, 97239, United States

Location

Sidney Kimmel Cancer Center, Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute and Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence; Breast Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasm Metastasis; Lung Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Neoplasms; Uterine Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes

Study Officials

• Jackie Walling, MBChB, PhD

  Lyell Immunopharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label, dose-escalation and -expansion study

Study Record Dates

• First Submitted: February 18, 2022
• First Posted: March 10, 2022
• Study Start: March 29, 2022
• Primary Completion: November 27, 2024
• Study Completion: November 27, 2024
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)