A Study to Investigate LYL797 in Adults With Solid Tumors

June 27, 2025 updated by: Lyell Immunopharma, Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • California
      • Santa Monica, California, United States, 90404
        • University of California, Los Angeles
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Miami, Florida, United States, 33136
        • University of Miami
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Sidney Kimmel Cancer Center, Jefferson University Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute and Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital, Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

IInclusion 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate incidence of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 2 years
Incidence of treatment-emergent adverse events (TEAEs)
Up to 2 years
Evaluate severity of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 2 years
Severity of treatment-emergent adverse events (TEAEs)
Up to 2 years
Determine recommended Phase 2 Dose (RP2D)
Time Frame: Up to 2 years
Dose-escalation phase to determine the recommended Phase 2 dose
Up to 2 years
Evaluate incidence of dose-limiting toxicities (DLTs)
Time Frame: Up to 28 days
Incidence of dose-limiting toxicities (DLTs)
Up to 28 days

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
Time Frame: Up to 2 years
Overall response rate (ORR) by RECIST, version 1.1
Up to 2 years
Evaluate duration of response (DOR)
Time Frame: Up to 2 years
Duration of response (DOR)
Up to 2 years
Evaluate progression-free survival (PFS)
Time Frame: Up to 2 years
Progression-free survival (PFS)
Up to 2 years
Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples
Time Frame: Up to 2 years
Maximum concentration of LYL797 (Cmax)
Up to 2 years
Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples
Time Frame: Up to 2 years
Time to Cmax (Tmax)
Up to 2 years
Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)
Time Frame: Up to 2 years
Area under the concentration-time curve (AUC)
Up to 2 years
Evaluate overall survival (OS)
Time Frame: Up to 2 years
Overall Survival (OS)
Up to 2 years
Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples
Time Frame: Up to 2 years
Time to last detectable LYL797, Tlast
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lyell Immunopharma, Inc.

Investigators

  • Study Director: Jackie Walling, MBChB, PhD, Lyell Immunopharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2022

Primary Completion (Actual)

November 27, 2024

Study Completion (Actual)

November 27, 2024

Study Registration Dates

First Submitted

February 18, 2022

First Submitted That Met QC Criteria

March 9, 2022

First Posted (Actual)

March 10, 2022

Study Record Updates

Last Update Posted (Estimated)

July 1, 2025

Last Update Submitted That Met QC Criteria

June 27, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LYL797-101

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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