A First-in-human (FIH), Phase 1 Study of ML261, an Autologous Potency Enhanced Anti-DLL3 CAR T Cell Therapy, in Participants With R/R SCLC or Select NECs (SPECTRAL-1) (SPECTRAL-1)

A Phase 1 First-In-Human Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of ML261, an Autologous Anti-DLL3 CAR + CARD11-PIK3R3 Fusion T Cell Therapy, in Participants With Relapsed/Refractory Small Cell Lung Cancer or Select Neuroendocrine Carcinomas

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

Study Overview

• Status: Not yet recruiting
• Conditions: Neuroendocrine Prostate Cancer (NEPC); Extrapulmonary Neuroendocrine Carcinoma (EP-NEC); Small Cell Lung Cancer (SCLC ); Gastroenteropancreatic NEC (GEP NEC)
• Intervention / Treatment: Biological: ML261

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Moonlight Bio Clinical Team; Phone Number: 206-647-6168; Email: MLTrials@moonlightbio.us

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
      • Principal Investigator: Martin Gutierrez, MD
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
      • Principal Investigator: Salman Punekar, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI)
      • Principal Investigator: Melissa Johnson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• ≥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%.
• Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1
• Life expectancy ≥12 weeks
• Have adequate hematologic and end-organ function

Exclusion Criteria:

• 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.
• Participants with toxicities (as a result of prior anti-cancer therapy) which have not recovered to baseline or CTCAE v5.0 <Grade 2, except for adverse events (AEs) not considered a likely safety risk: (e.g., alopecia, neuropathy, non-clinically relevant laboratory abnormalities).
• Symptomatic ascites or effusions (pleural or pericardial) requiring intermittent drainage.
• History of any other malignancy known to be active, with the exception of completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, ductal carcinoma in situ, early-stage prostate cancer that has been adequately treated, and other cancers from which the participant has been disease free for 3 years or longer or does not require treatment and in the opinion of investigator after discussion with the medical monitor are not likely to impact the patient's life expectancy.
• One or more of the following cardiac criteria: Unstable angina, Myocardial infarction within 6 months prior to Screening, New York Heart Association Class III to IV heart failure, clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block or third-degree heart block)
• Acute venous thromboembolism (VTE). VTEs without hemodynamic compromise, treated with stable doses of anticoagulants are allowed.

• Presence of clinically significant CNS pathology:

  • seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, or cerebellar disease. History of these disorders requires discussion with the medical monitor.
  • Presence of clinically active psychosis.
  • Known brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the first dose of any study drug administration.
• Active systemic autoimmune disease or any other condition that requires, or is anticipated to require, systemic treatment with steroids or other systemic immunosuppressive agents, or participants who have received such agents within 4 weeks of leukapheresis and ML261 administration (further details provided in protocol body).
• Evidence of interstitial lung disease (such as idiopathic pulmonary fibrosis) or active pneumonitis of any etiology requiring treatment.
• Any active infection (defined as symptoms, signs, or radiographic) of bacterial, viral, or fungal or unknown etiology requiring systemic therapy within 14 days of leukapheresis. Participants with clinical and/or laboratory evidence of persistent infection will be excluded.
• Uncontrolled medical, psychological/psychiatric, or social condition that would interfere with the participant's participation or compromise the objectives of the study in the opinion of the Investigator and/or the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ML261; DLL3-Directed Chimeric Antigen Receptor T cells (CAR T)	Biological: ML261; DLL3 directed autologous Chimeric Antigen Receptor T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Through study completion; up to 2 years
Characterize the molecular pharmacokinetic (PK) profile of ML261 after dosing	Measurement of ML261 associated vector copy number (VCN) in peripheral blood over time	Through study completion; up to 2 years
Evaluate the preliminary efficacy of ML261 after dosing	Measured by Response Evaluation Criteria In Solid Tumors (RECIST v1.1)	Through study completion; up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the immunogenicity of ML261 after dosing	Number of participants with presence of anti-ML261 antibodies over time	Through study completion; up to 2 years

Collaborators and Investigators

• Sponsor: Moonlight Bio, Inc

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: CAR T; DLL3; Neuroendocrine carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine
• Other Study ID Numbers: ML261-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No