Advanced Breast Cancer, Advanced Lung Carcinoma, Endometrial Cancer, Endometrioid Tumor, Fallopian Tube Cancer, High Grade Serous Carcinoma, Non-Small Cell Carcinoma of Lung, TNM Stage 4, Non-small Cell Lung Cancer, Non Small Cell Lung Cancer, Non Small Cell Lung Cancer Metastatic, NSCLC, NSCLC, Recurrent, NSCLC Stage IV, Ovarian Cancer, Ovarian Epithelial Cancer, Platinum-resistant Ovarian Cancer, Primary Peritoneal Carcinoma, Recurrent Breast Cancer, Recurrent NSCLC, Relapsed Cancer, Relapse/Recurrence, TNBC - Triple-Negative Breast Cancer, Triple Negative Breast Cancer
Conditions
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
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.
Interventions
BIOLOGICALLYL797
LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy
Sponsors
Lyell Immunopharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label, dose-escalation and -expansion study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine recommended Phase 2 Dose (RP2D) | Up to 2 years | Dose-escalation phase to determine the recommended Phase 2 dose |
| Evaluate incidence of dose-limiting toxicities (DLTs) | Up to 28 days | Incidence of dose-limiting toxicities (DLTs) |
| Evaluate incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years | Incidence of treatment-emergent adverse events (TEAEs) |
| Evaluate severity of treatment-emergent adverse events (TEAEs) | Up to 2 years | Severity of treatment-emergent adverse events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples | Up to 2 years | Maximum concentration of LYL797 (Cmax) |
| Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples | Up to 2 years | Time to Cmax (Tmax) |
| Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1 | Up to 2 years | Overall response rate (ORR) by RECIST, version 1.1 |
| Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples | Up to 2 years | Time to last detectable LYL797, Tlast |
| Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB) | Up to 2 years | Area under the concentration-time curve (AUC) |
| Evaluate duration of response (DOR) | Up to 2 years | Duration of response (DOR) |
| Evaluate progression-free survival (PFS) | Up to 2 years | Progression-free survival (PFS) |
| Evaluate overall survival (OS) | Up to 2 years | Overall Survival (OS) |
Countries
United States
Outcome results
None listed