A Phase I/II Trial of ALETA-001 for the Treatment of Participants with B-cell Malignancies

Inclusion Criteria:

• Aged 16 years or over.

• Written informed consent and capable of co-operating with ALETA-001 administrationand follow-up.

• Confirmed diagnosis of NHL according to World Health Organization (WHO) 2016criteria.

• Received one of the following approved anti-CD19 CAR T-cell therapies: Kymriah,Yescarta and Tecartus.

• Objectively evaluable or measurable disease at 4 weeks post CAR T, whichdemonstrates inadequate or incomplete response or progressive disease if there is areasonable expectation of deriving benefit from trial treatment, or- initialresponse followed by relapse within 9 months assessed according to Lugano criteria.

• Eastern Cooperative Oncology Group performance status of 0, 1 or 2 followinganti-CD19 CAR T-cell treatment.

• Haematological and biochemical indices within protocol specified ranges.

Exclusion Criteria:

• Participants who have received any other anti-cancer treatment post-CAR T.

• Concurrent radiotherapy (except for palliative reasons).

• Potential participants who experienced any of the following because of the initialCAR T-cell treatment: Grade 4 ICANs, Grade >=3 ICANs persisting beyond 7 days anddespite optimal supportive therapy. Grade 4 CRS, Grade 3 CRS persisting beyond 7days and despite optimal supportive therapy, any Grade 2 ICANs or CRS must be fullyresolved.

• Any ongoing toxic manifestation of previous anti-cancer treatment that, in theopinion of the Investigator, should exclude the participant.

• Active or previous malignancies of other types that, in the opinion of theInvestigator, should exclude the participant. Exceptions include adequately treatedcone biopsied in situ carcinoma of the cervix uteri and basal or squamous cellcarcinoma of the skin and patients with asymptomatic prostate cancer without knownmetastatic disease and with no requirement for therapy or who require only hormonaltherapy and have had normal prostate specific antigen for >1 year prior to the startof therapy. Cancer survivors, who have undergone potentially curative therapy for aprior malignancy, have no evidence of that disease for 2 years or more and aredeemed at negligible risk for recurrence, are eligible for the trial.

• Ongoing need for systemic immunosuppressive therapy other than replacement dose ofcorticosteroids. Intermittent topical, inhaled or intra-nasal corticosteroids arepermitted.

• Presence of active infections and/ or inflammatory disease requiring activemanagement.

• Documented current central nervous system involvement by lymphoma.

• Women of childbearing potential (or are already pregnant or lactating) unlesswilling to adhere to protocol-defined contraceptive requirements.

• Male patients with partners of childbearing potential unless willing to adhere toprotocol-defined contraceptive requirements.

• Major thoracic or abdominal surgery from which the participant has not yetrecovered.

• At high medical risk because of non-malignant systemic disease including activeuncontrolled infection.

• Hypersensitivity to any of the ingredients/excipients in ALETA-001

• Participation in another interventional clinical trial, whilst taking part in thistrial of ALETA-001. Participation in an observational trial or interventionalclinical trial that does not involve administration of an IMP and that would notplace an unacceptable burden on the participant, in the opinion of the Investigatorand CDD, would be acceptable.

• Participants with any congenital or acquired immunodeficiency syndrome or who arereceiving immunosuppressive therapy (including any dose of systemiccorticosteroids), or who are immunosuppressed post organ transplant. However,participants receiving inhaled corticosteroids and participants with a history ofallergy (other than anaphylaxis) are eligible, as are participants with a history ofautoimmune disease.

• Any other condition that, in the Investigator's opinion, would mean that the trialis not in the best interests of the participant.