This is a first-in-human (FIH), open-label, Phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of ML261, an autologous potency enhanced anti-DLL3 CAR T cell therapy, in participants with R/R SCLC or select NECs
≥18 years of age at the time of signing the ICF
Have been previously treated with at least one line of systemic standard of care (SOC) anti-cancer therapy for their respective cancer indication. Participants with locally advanced disease who are eligible for curative resection will be excluded.
Have documented radiological disease progression/relapse during or after their most recent line of anti-cancer therapy with measurable disease on imaging, as assessed by RECIST v1.1
Have histologically and/or cytologically confirmed diagnosis of select advanced or metastatic R/R solid tumor malignancy in one of the following: R/R SCLC, R/R GEP-NEC, R/R high-grade NEPC, R/R epNEC with biopsy-documented DLL3 expression on archival tissue or fresh biopsy by local or central assessment. CNS NEC is excluded. Participants with mixed histologies for any of these indications qualify if the small cell/neuroendocrine tumor cell percentage is > 50%, except for high-grade NEPC where neuroendocrine component must be > 20%.
Previous systemic anti-cancer therapies within the timeframes, as specified in the protocol.
Prior exposure/treatment with DLL3-targeted CAR T therapy or any other genetically engineered adoptive T cell therapy.
Prior allogeneic organ transplant (including allogeneic bone marrow transplant).
Major surgical procedure within 4 weeks of the first dose of any study drug administration or anticipated to be in need of a major surgical procedure during the course of study.
Sequential
ML261
Biological/VaccineDLL3 directed autologous Chimeric Antigen Receptor T cells
Incidence of dose-limiting toxicities (DLTs) listed during the DLT observation period
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) or American Society for Transplantation and Cell Therapy (ASTCT) criteria
Incidence of treatment-emergent AEs (TEAEs), Grade ≥3 TEAEs, serious AEs (SAEs), and AEs of special interest (AESIs). Clinically significant laboratory abnormalities / changes from baseline in safety laboratory test results
Graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0) or American Society for Transplantation and Cell Therapy (ASTCT) criteria (for grading CRS and ICANS)
Characterize the molecular pharmacokinetic (PK) profile of ML261 after dosing
Measurement of ML261 associated vector copy number (VCN) in peripheral blood over time
Evaluate the preliminary efficacy of ML261 after dosing
Measured by Response Evaluation Criteria In Solid Tumors (RECIST v1.1)
Evaluate the immunogenicity of ML261 after dosing
Number of participants with presence of anti-ML261 antibodies over time
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