Background While Bruton's Tyrosine Kinase (BTK) inhibitors approved for CLL/SLL (ibrutinib, acalabrutinib) can mediate durable responses in some patients, relapses are seen primarily as a result of acquired mutations in BTK enzyme and/or phospholipase C gamma 2. Adoptive cell transfer of IOV-2001, a polyclonal and nongenetically modified autologous T-cell infusion product, is being investigated as a therapy option for CLL/SLL patients who are progressing or have progressed on ibrutinib or acalabrutinib. Methods IOV-CLL-01 (NCT04155710) is a First in Patient, Phase 1/2, open-label, multi-cohort, dose-finding study designed to evaluate the safety and efficacy of IOV-2001, in patients with CLL/SLL (Table 1). 50 ml of blood obtained from patients is used to generate Peripheral Blood Lymphocytes (PBLs). PBLs are result of expansion of T-cells in a 9-day manufacturing process at a centralized GMP facility. The product is then cryopreserved and sent back to the treatment center for infusion to the patient. IOV-2001 is a one-time administration cell therapy which involves a preparative regimen of lymphodepleting chemotherapy consisting of cyclophosphamide IV 500 mg/m2 and fludarabine IV 30 mg/m2 for 3 days followed by 2 days of rest. IOV-2001 is administered as a single infusion, followed by up to 6 doses of IL-2. Key eligibility includes diagnosed CLL/SLL patients (18 to 70 years of age) with radiographically measurable disease; and ECOG PS of 0-1, along with specifics per Table 1. The primary objective for Phase 1 is to determine the RP2D, and for Phase 2 is to evaluate the Investigator-assessed efficacy of IOV-2001 at RP2D followed by IL-2.

Table 1.

Overview of IOV-CLL-2001

PhaseStudy PopulationCohort Test Product, Dose Regimen, and Route of Administration
Phase 1 CLL / SLL that has relapsed or is relapsing on ibrutinib or acalabrutinib Dose-finding with IOV-2001 dose de-escalation guided by DLT observations: 
  -Cohort 1a: IOV-2001, followed by ≤6 doses of SC low-dose IL-2 (9 MIU) every 8-12 hours 
  -Cohort 1b: IOV-2001, followed by ≤6 doses of IV high-dose (600,000 IU/kg) every 8-12 hours 
Phase 2  IOV-2001 RP2D dose, followed by ≤6 doses of the selected IL-2 dose: 
  -Cohort 2: with del(17p) and/or TP53 mutation 
  -Cohort 3: without del(17p) and/or TP53 mutation 
PhaseStudy PopulationCohort Test Product, Dose Regimen, and Route of Administration
Phase 1 CLL / SLL that has relapsed or is relapsing on ibrutinib or acalabrutinib Dose-finding with IOV-2001 dose de-escalation guided by DLT observations: 
  -Cohort 1a: IOV-2001, followed by ≤6 doses of SC low-dose IL-2 (9 MIU) every 8-12 hours 
  -Cohort 1b: IOV-2001, followed by ≤6 doses of IV high-dose (600,000 IU/kg) every 8-12 hours 
Phase 2  IOV-2001 RP2D dose, followed by ≤6 doses of the selected IL-2 dose: 
  -Cohort 2: with del(17p) and/or TP53 mutation 
  -Cohort 3: without del(17p) and/or TP53 mutation 

Citation Format: Meixiao Long, Jennifer Woyach, Javier Pinilla-Ibarz, Deborah M. Stephens, Alex Cacovean, Rana Fiaz, Zelanna Goldberg, Madan Jagasia, Friedrich Graf Finckenstein, Maria Fardis, John C. Byrd. A Phase 1/2 study evaluating the safety and efficacy of IOV-2001 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT244.