This is a Phase I/II multicentre, open-label trial designed to evaluate the efficacy, safety, tolerability, timing of administration and pharmacokinetics (PK) of a novel chimeric antigen receptor (CAR) T-cell engager, ALETA-001, administered by intravenous (IV) infusion as a single agent every 2 weeks in participants with B-cell malignancies post CD19 CAR T-cell therapy. This first in human study is divided into 2 parts: a safety lead-in phase (Phase I) and a dose expansion phase (Phase II). Different dose levels of ALETA-001 and timing of administration will be evaluated in Phase I in order to define a recommended dosing level and time of administration for Phase II. Phase II will further evaluate the safety, PK and therapeutic activity of ALETA-001.
Aged 16 years or over.
Written (signed and dated) informed consent and be capable of co-operating with ALETA-001 administration and follow-up.
Confirmed diagnosis of B-cell NHL according to World Health Organization (WHO) 2016 criteria.
Eastern Cooperative Oncology Group performance status of 0, 1 or 2.
Active or previous malignancies of other types that, in the opinion of the Investigator, should exclude the participant. Exceptions include adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and patients with asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or who require only hormonal therapy and have had normal prostate specific antigen for >1 year prior to the start of therapy. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 2 years or more and are deemed at negligible risk for recurrence, are eligible for the trial.
Any ongoing toxic manifestation of previous anti-cancer treatment that, in the opinion of the Investigator, should exclude the participant.
Ongoing need for systemic immunosuppressive therapy other than replacement dose of corticosteroids. Intermittent topical, inhaled or intranasal corticosteroids are permitted.
Presence of active infections and/ or inflammatory disease requiring active management.
Single group
ALETA-001
DrugALETA-001 will be administered intravenously (IV) every two weeks.
Dose level of ALETA-001 and timing of administration for use in Dose Expansion (Safety Lead-in Phase).
Determine a dose level that is deemed tolerable and timing of administration based on available safety and pharmacodynamic data.
Number of Participants who experience dose limiting toxicities (DLTs).
DLTs will be assessed up to Day 28 and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the 28 days of the first dose of ALETA-001.
Number of Participants who experience Grade 3, 4 or 5 related adverse event (AEs).
Related AEs are those considered by the investigator to be possibly, probably or highly probably related to ALETA-001. Events of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity (ICANS) are graded according to the American Society for Transplantation and Cellular Therapy grading criteria. All other AEs are graded according to the Common Terminology Criteria for AEs (CTCAE) Version 5.0.
Best Overall Response (Dose Expansion Phase).
Best Overall Response according to Lugano criteria (Cheson, Journal of Clinical Oncology, 2014), the number of participants taking part in the Dose Expansion Phase with best overall response of complete response (CR), partial response (PR), no response or stable disease (SD/NR), and progressive disease (PD).
Best Overall Response (Safety Lead-in Phase).
Best Overall Response according to Lugano criteria, the number of participants taking part in the Safety Lead-in Phase with best overall response of complete response (CR), partial response (PR), no response or stable disease (SD), and progressive disease (PD).
Progression-Free Survival (PFS) (Safety Lead-in Phase).
Median PFS measured from first dose of ALETA-001 to date of progression according to Lugano criteria or date of death without a previous progression recorded.
Time to Progression (TTP) (Safety Lead-in Phase).
Median TTP measured from first dose of ALETA-001 to date of progression according to Lugano criteria. Participants who die without recorded progression will be censored.
Overall Survival (OS) (Safety Lead-in Phase).
Median OS measured from first dose of ALETA-001 to date of death due to any cause or to the date of censoring at the last time the participant was known to be alive.
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Cancer Research UK
Lead sponsor
Aleta BioTherapeutics
Collaborator
