Pipeline Reprioritization

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.

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.

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