A Study of Armored CAR T Cells in People With Cancer

A Phase I Trial for R/R MetAstatic DLL3+ Cancers Utilizing Armored CAR T Cells (ARMADA)

The purpose of this study is to test the safety of DLL3-SAVVYZ-IL18 in people with DLL3+ cancer.

Inclusion Criteria:

Participant Inclusion: 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, glioblastoma multiforme, skin NETs, NETs of unknown primary, or other tumor confirmed positive for DLL3 by IHC
  • Any disease status is eligible for collection.
  • DLL3 expression detected by IHC
  • Off any immunosuppressive agents for 14 days prior to collection (physiologic dose of corticosteroids is acceptable)

Participant Inclusion: 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.

• Prior treatment should include an approved platinum-based regimen with/without ICI therapy if applicable to their disease.

• Other advanced tumors are eligible if there is documented progression and/or relapse after appropriate frontline treatment(s) and otherwise meet eligibility criteria.

• At least 1 measurable lesion as defined per modified RECIST 1.1 within 21 days prior to first dose of LDC.

• Age > 18 years old at the time of signing the informed consent.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Minimum life expectancy of 12 weeks.

• Participants previously treated with DLL3-specific therapies (i.e. antibody-drug conjugates, T-cell engager molecules) are permitted.

• History of CNS disease is permitted if previously treated, stable (without evidence of radiographic progression for at least 14 days prior to the first dose of LDC and any neurologic symptoms have returned to baseline), and/or asymptomatic.

• Adequate organ function is required, defined as follows:

  • Hematologic: Hgb > 8 g/dL, platelets > 75 x103/ul
  • Hepatic: Serum total bilirubin ≤1.5 mg/dL (unless Gilbert's syndrome), albumin > 3 g/dL.
  • Hepatic: ALT and AST < 5 times the upper limit of normal unless thought to be disease-related.
  • Renal: serum creatinine < 2.0 mg/dL (> 18 years) or ≤ 2.5 x institutional upper limit of normal (ULN) for age
  • If serum creatinine is outside the normal range, then CrCl > 40 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.73m2) > 40% of predicted normal for age.
  • Cardiac: LVEF ≥ 50% by resting echocardiogram
  • Pulmonary: Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by pulse oximetry

Exclusion Criteria:

Participant Exclusion: Collection of T cells (Part A)

• Pregnant or lactating women; women of childbearing age, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception while receiving study treatment and for at least 12 months after all treatment is finished.

• Sexually active males, unless they are willing to use a condom during intercourse while receiving study treatment and for at least 12 months after all treatment is finished.

• Any systemic anti-cancer therapy within 14 days or at least 4 half lives prior to time of T cell collection, whichever is shorter.

• Radiation therapy completed within 7 days prior to time of T cell collection.

• Uncontrolled, symptomatic, intercurrent infection

• 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.

• Positive serologic test results for HIV.

• Patients with active hepatitis B infection (as manifested by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen)

• Patients with active hepatitis C infection (as manifested by detectable hepatitis C virus RNA by PCR)

Participant Exclusion: 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.

• Any autoimmune disease requiring active systemic immunosuppression.

  • Use of physiologic steroid replacement for adrenal insufficiency and inhaled corticosteroids are permitted

• Pregnant or lactating women

• Uncontrolled, symptomatic, intercurrent infection

• CNS disease that is symptomatic (including use of steroids within 7-days prior to first dose of LDC) or new/enlarging. Patients with treated brain metastasis are allowed if completed at least 2 weeks prior to enrollment and documented stable/asymptomatic disease since off steroids.

• Patient/parent/guardian unable to give informed consent.

• 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.