Clinical trial NCT05274451: A Study to Investigate LYL797 in Adults With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: Lyell Immunopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open-label, dose-escalation and -expansion study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate incidence of dose-limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Evaluate incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Evaluate severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Determine recommended Phase 2 Dose (RP2D)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1
timeFrame: Up to 2 years
measure: Evaluate duration of response (DOR)
timeFrame: Up to 2 years
measure: Evaluate progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Evaluate overall survival (OS)
timeFrame: Up to 2 years
measure: Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples
timeFrame: Up to 2 years
measure: Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples
timeFrame: Up to 2 years
measure: Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)
timeFrame: Up to 2 years
measure: Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Santa Monica
country: United States
facility: University of California, Los Angeles
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center, Jefferson University Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute and Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital, Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Lyell Immunopharma, Inc.
name: Jackie Walling, MBChB, PhD
role: STUDY_DIRECTOR
References: