A Study of Armored Chimeric Antigen Receptor T Cells for the Treatment of DLL3+ Cancers, ARMADA Trial
This phase I trial studies the side effects and best dose of DLL3-SAVVYZ-IL18 chimeric antigen receptor (CAR) T cells when given after cyclophosphamide and fludarabine in treating patients with DLL3+ cancers. DLL3-SAVVYZ-IL18 CAR T cells are a type of CAR T cell therapy. DLL3-SAVVYZ-IL18 is made in the laboratory using a patient's collected white blood cells (T cells). T cells are important protective cells of the immune system. The T cells in DLL3-SAVVYZ-IL18 have been genetically modified (changes are made to the DNA or genes) to help them work against tumor cells. A virus (retrovirus) is used to introduce a gene that creates a protein (called a chimeric antigen receptor or CAR) on the surface of T cells to identify and kill tumor cells. The retrovirus then becomes inactive. DLL3-SAVVYZ-IL18 can recognize a protein called DLL3, which is found on the surface of tumor cells, and destroy those cells. T-cell therapies like DLL3-SAVVYZ-IL18 are called CAR T-cell therapies. Before patients receive the DLL3-SAVVYZ-IL18 CAR T cells chemotherapy with cyclophosphamide and fludarabine is given to briefly weaken (suppress) the immune system and prepare the body for receiving the DLL3-SAVVYZ-IL18 CAR T cells. Giving DLL3-SAVVYZ-IL18 CAR T cells after cyclophosphamide and fludarabine may be safe, tolerable, and/or effective in treating patients with DLL3+ cancers.
Inclusion Criteria
- COLLECTION OF T CELLS (PART A): History of DLL3+ neuroendocrine tumors * Includes patients with histologically confirmed SCLC, as well other advanced neuroendocrine tumors (NETs), including large cell neuroendocrine carcinomas (LCNECs), gastroenteropancreatic NETs (GEP-NETs), laryngeal NETs, genitourinary (GU) tract NETs, neuroendocrine prostate cancers (NEPCs), gynecological tract NETs, neuroblastomas, salivary NETs, skin NETs, NETs of unknown primary, or other tumor confirmed positive for DLL3 by immunohistochemistry (IHC)
- COLLECTION OF T CELLS (PART A): Any disease status is eligible for collection
- COLLECTION OF T CELLS (PART A): DLL3 expression detected by IHC using archival tumor tissue or tissue obtained from a biopsy performed as part of standard clinical care. No new biopsy will be performed solely for DLL3 IHC eligibility testing
- COLLECTION OF T CELLS (PART A): Off any immunosuppressive agents for 14 days prior to collection (physiologic dose of corticosteroids is acceptable)
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Any participant with histologically confirmed SCLC or DLL3 positive tumor who has had one line of approved systemic therapy for limited or extensive stage disease and has progressed or is no longer deriving benefit or standard treatment is no longer tolerable or declines further standard treatment
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Prior treatment should include an approved platinum-based regimen with/without immune checkpoint inhibitor (ICI) therapy if applicable to their disease
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Other advanced tumors are eligible if there is documented progression and/or relapse after appropriate frontline treatment(s) and otherwise meet eligibility criteria
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): At least 1 measurable lesion as defined per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 21 days prior to first dose of lymphodepleting chemotherapy (LDC)
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Age > 18 years old at the time of signing the informed consent
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Minimum life expectancy of 12 weeks
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Participants previously treated with DLL3-specific therapies (i.e. antibody-drug conjugates, T-cell engager molecules) are permitted
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): History of central nervous system (CNS) metastatic disease is permitted if previously treated and stable, defined as no evidence of radiographic progression for at least 4 weeks prior to the first dose of LDC, with any neurologic symptoms returned to baseline. Asymptomatic CNS metastatic disease must also be radiographically stable for at least 4 weeks prior to the first dose of LDC
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Hemoglobin (Hgb) > 9 g/dL
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Platelets > 75 x10^3/ul
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Serum total bilirubin ≤ 1.5 mg/dL (unless Gilbert’s syndrome)
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Albumin > 3 g/dL
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Alanine aminotransferase (ALT) < 5 times the upper limit of normal unless thought to be disease-related
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Aspartate aminotransferase (AST) < 5 times the upper limit of normal unless thought to be disease-related
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Serum creatinine < 2.0 mg/dL (> 18 years) or ≤ 2.5 x institutional upper limit of normal (ULN) for age
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): If serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 40 mL/min/1.73m^2 (calculated or estimated) or glomerular filtration rate (GFR) (mL/min/1.73m^2) > 40% of predicted normal for age
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Left ventricular ejection fraction (LVEF) ≥ 50% by resting echocardiogram
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by pulse oximetry
Exclusion Criteria
- COLLECTION OF T CELLS (PART A): Pregnant or lactating female participants; female participants of reproductive potential, unless they agree to use a highly effective method of contraception or abstain from heterosexual intercourse while receiving study treatment and for at least 12 months after all treatment is finished
- COLLECTION OF T CELLS (PART A): Sexually active male participants with female partners of reproductive potential, unless they agree to use a condom during intercourse and their female partners use a highly effective method of contraception while the participant is receiving study treatment and for at least 12 months after all treatment is finished
- COLLECTION OF T CELLS (PART A): Primary CNS malignancies, including glioblastoma multiforme (GBM), are excluded
- COLLECTION OF T CELLS (PART A): Any systemic anti-cancer therapy within 14 days or at least 4 half lives prior to time of T cell collection, whichever is shorter
- COLLECTION OF T CELLS (PART A): Radiation therapy completed within 7 days prior to time of T cell collection
- COLLECTION OF T CELLS (PART A): Uncontrolled, symptomatic, intercurrent infection
- COLLECTION OF T CELLS (PART A): Patients with following cardiac conditions will be excluded: * New York Heart Association (NYHA) stage III or IV congestive heart failure * Myocardial infarction ≤ 6 months prior to enrollment
- COLLECTION OF T CELLS (PART A): Positive serologic test results for HIV
- COLLECTION OF T CELLS (PART A): Patients with active hepatitis B infection (as manifested by either detectable hepatitis B virus deoxyribonucleic acid [DNA] by polymerase chain reaction [PCR] and/or positivity for hepatitis B surface antigen)
- COLLECTION OF T CELLS (PART A): Patients with active hepatitis C infection (as manifested by detectable hepatitis C virus ribonucleic acid [RNA] by PCR)
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): For prior immune related adverse events (irAEs): * Unresolved pneumonitis of any grade or history of any grade ICI-mediated CNS toxicities * Other unresolved toxicity grade 2 or higher, excluding hypothyroidism
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Any autoimmune disease requiring active systemic immunosuppression * Use of physiologic steroid replacement for adrenal insufficiency and inhaled corticosteroids are permitted
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Pregnant or lactating female participants; female participants of reproductive potential, unless they agree to use a highly effective method of contraception or abstain from heterosexual intercourse while receiving study treatment and for at least 12 months after all treatment is finished
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Sexually active male participants with female partners of reproductive potential, unless they agree to use a condom during intercourse and their female partners use a highly effective method of contraception while the participant is receiving study treatment and for at least 12 months after all treatment is finished
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Primary CNS malignancies, including glioblastoma multiforme (GBM), are excluded
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): CNS metastatic disease that is symptomatic (including use of steroids within 7 days prior to the first dose of LDC) or new/enlarging is excluded. Patients with treated brain metastases are permitted if treatment was completed at least 4 weeks prior to the first dose of LDC and the disease has remained radiographically stable for at least 4 weeks prior to the first dose of LDC, with neurologic symptoms returned to baseline
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Uncontrolled, symptomatic, intercurrent infection
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Patient/parent/guardian unable to give informed consent
- TREATMENT WITH DLL3-SAVVYZ-IL18 CAR T CELLS (PART B): Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study; conditions that in the principal investigator’s opinion might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07783477.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. To determine the toxicity and maximum tolerated dose of anti-DLL3-SAVVYZ-IL-18-expressing CAR T-cells (DLL3-SAVVYZ-IL18 CAR T cells) in participants with lung small cell carcinoma (SCLC) or other DLL3-expressing tumors.
SECONDARY OBJECTIVES:
I. To assess the anti-tumor efficacy of DLL3-SAVVYZ-IL18 CAR T cells.
II. To assess the in vivo persistence of DLL3-SAVVYZ-IL18 CAR T cells.
III. To estimate the proportion of patients who are unable to proceed to infusion following collection.
EXPLORATORY OBJECTIVES:
I. To assess the capacity of DLL3-SAVVYZ-IL18 CAR T cells to modify the tumor microenvironment and patient’s immune profile.
II. To assess the capacity of DLL3-SAVVYZ-IL18 CAR T cells to enhance the expansion of endogenous CAR-negative tumor-targeted T cells.
OUTLINE: This is a dose-escalation study of DLL3-SAVVYZ-IL18 CAR T cells in combination with cyclophosphamide and fludarabine.
Patients undergo leukapheresis on study for the manufacturing of DLL3-SAVVYZ-IL18 CAR T cells. Patients then receive cyclophosphamide intravenously (IV) over 1 hour and fludarabine IV over 30 minutes on days -5, -4, and -3. Starting on day 0, patients also receive DLL3-SAVVYZ-IL18 CAR T cells IV over 15-120 minutes, administered over 1-3 days at the discretion of the treating physician, in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) during screening and tumor biopsy, blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) throughout the study.
After completion of study treatment, patients are followed up at days 1-7, 14, 21, 28, 42, and 56, months 3, 4, 5, and 6, then every 3 months up to 2 years followed by every year for up to 15 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAdam Schoenfeld
- Primary ID26-062
- Secondary IDsNCI-2026-06605
- ClinicalTrials.gov IDNCT07783477