A Study to Investigate LYL797 in Adults With Solid Tumors

February 29, 2024 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) 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.

Study Overview

Status

Recruiting

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-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.

Study Type

Interventional

Enrollment (Estimated)

54

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 Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Brenda Ernst, MD
          • Phone Number: 800-446-2279
    • California
      • Santa Monica, California, United States, 90404
        • Recruiting
        • University of California, Los Angeles
        • Contact:
          • Jonathan W Goldman, MD
          • Phone Number: 310-633-8400
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale New Haven Hospital
        • Contact:
          • Michael Hurwitz, MD
          • Phone Number: 203-785-4095
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University
        • Contact:
          • Chul Kim, MD
          • Phone Number: 202-444-2223
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Hemant Murthy, MD
          • Phone Number: 855-776-0015
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
          • Amer Beitinjaneh, MD
          • Phone Number: 305-243-5302
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago
        • Contact:
          • Michael Bishop, MD
          • Phone Number: 773-702-4400
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Contact:
          • Hirva Mamdani, MD
          • Phone Number: 800-527-6266
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Roberto Leon Ferre, MD
          • Phone Number: 507-538-3270
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center
        • Contact:
          • Roberto Sica, MD
          • Phone Number: 718-920-4321
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Roisin O'Cearbhaill, MD
          • Phone Number: 833-267-2258
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma
        • Contact:
          • Manu Pandey, MD
          • Phone Number: 405-271-8299
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University Hospital
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Cancer Center, Jefferson University Hospital
        • Contact:
          • Babar Bashir, MD
          • Phone Number: 215-955-1661
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute and Tennessee Oncology
        • Contact:
          • David Spigel, MD
          • Phone Number: 844-482-4812
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
          • Haven Garber, MD
          • Phone Number: 833-955-3090
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Center
        • Contact:
          • Jennifer Specht, MD
          • Phone Number: 855-557-0555
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital, Medical College of Wisconsin
        • Contact:
          • Lubna Chaudhary, MD
          • Phone Number: 414-805-3666

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

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

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 dose-limiting toxicities (DLTs)
Time Frame: Up to 2 years
Incidence of dose-limiting toxicities (DLTs)
Up to 2 years
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

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 anti-tumor activity of LYL797 based on complete response (CR) rate by RECIST, version 1.1
Time Frame: Up to 2 years
Complete response (CR) rate 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 overall survival (OS)
Time Frame: Up to 2 years
Overall survival (OS)
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 Persistence of LYL797 CAR T cells in peripheral blood samples
Time Frame: Up to 2 years
Persistence of LYL797 in PB
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, MD, 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 (Estimated)

March 1, 2025

Study Completion (Estimated)

September 1, 2026

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 (Actual)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

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

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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