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.
Brief Title
A Study to Investigate LYL797 in Adults With Solid Tumors
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.
Categories
Completion Date
Completion Date Type
Actual
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
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
* ≥ 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
Inclusion 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
* ≥ 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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05274451
Org Class
Industry
Org Full Name
Lyell Immunopharma, Inc.
Org Study Id
LYL797-101
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Incidence of dose-limiting toxicities (DLTs)
Outcome Measure
Evaluate incidence of dose-limiting toxicities (DLTs)
Outcome Time Frame
Up to 28 days
Outcome Description
Incidence of treatment-emergent adverse events (TEAEs)
Outcome Measure
Evaluate incidence of treatment-emergent adverse events (TEAEs)
Outcome Time Frame
Up to 2 years
Outcome Description
Severity of treatment-emergent adverse events (TEAEs)
Outcome Measure
Evaluate severity of treatment-emergent adverse events (TEAEs)
Outcome Time Frame
Up to 2 years
Outcome Description
Dose-escalation phase to determine the recommended Phase 2 dose
Outcome Measure
Determine recommended Phase 2 Dose (RP2D)
Outcome Time Frame
Up to 2 years
Secondary Outcomes
Outcome Description
Overall response rate (ORR) by RECIST, version 1.1
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1
Outcome Description
Duration of response (DOR)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate duration of response (DOR)
Outcome Description
Progression-free survival (PFS)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate progression-free survival (PFS)
Outcome Description
Overall Survival (OS)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate overall survival (OS)
Outcome Description
Maximum concentration of LYL797 (Cmax)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples
Outcome Description
Time to Cmax (Tmax)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples
Outcome Description
Area under the concentration-time curve (AUC)
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)
Outcome Description
Time to last detectable LYL797, Tlast
Outcome Time Frame
Up to 2 years
Outcome Measure
Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Roberto Alejandro Sica
Investigator Email
asica@montefiore.org