Sponsor's decision

This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous chimeric antigen receptor (CAR) T cells targeting both CD19 and CD22, manufactured with T-Charge(TM) process. CAR-T cells will be investigated as single agent in pediatric and adult acute lymphoblastic leukemia (ALL).

This is a phase I, open label, multicenter, dose escalation and expansion study of IMJ995. The study will investigate single agent IMJ995 in two independent groups of acute lymphoblastic leukemia (ALL) patients:

• Pediatric, adolescent and young adult (AYA) ALL patients up to 29 years old
• Adult ALL patients (≥30 years old) safety cohort The pediatric and AYA ALL group consists of two parts: a dose escalation part to evaluate feasibility, characterize safety and identify the recommended dose (RD) of IMJ995, and a dose expansion part to further characterize safety, cellular kinetics and assess preliminary antitumor activity. Once the RD of IMJ995 is determined for this group, the corresponding expansion part may commence.

Once the RD of IMJ995 is determined for the pediatric and AYA group, a safety cohort for adult ALL patients ≥30 years old may commence in parallel to the above mentioned expansion part.

Inclusion Criteria:

All patients:

• Evidence of CD19 and/or CD22 cell surface expression on B-ALL blasts in bone marrow or peripheral blood by flow cytometry at time of relapse or prior to study entry.

Pediatric, adolescent and young adult ALL patients:

• 1 - 29 years of age at the time of informed consent form (ICF) signature.
• Relapsed or refractory CD19+ and/or CD22+ ALL after 3 or more lines of treatment OR after allogeneic HCT.
• Must have received a CD19-directed CAR-T treatment (with or without blinatumomab), unless prior loss of CD19 cell surface expression occurred or have not been eligible for CD19 directed CAR-T treatment.
• Lansky (age < 16 years), Karnofsky (age 16-25 years) performance status ≥ 60%. ECOG (age >25 years) performance status that is either 0 or 1 at screening.

Adult ALL patients aged ≥30 years:

• ≥30 years of age at the time of informed consent form (ICF) signature.

• Refractory or relapsed CD19+ and/or CD22+ ALL including at least one of the following:

  • After allogeneic HCT
  • After 2 or more lines of treatment, including blinatumomab and/or inotuzumab
  • Primary refractory disease (defined as failure to achieve a CR at the end of at least 1 induction chemotherapy)
  • First relapse occurring within 12 months from first remission

• ECOG performance status that is either 0 or 1 at screening.

Exclusion Criteria:

• Allogeneic HCT within 12 weeks prior to screening.
• Presence of isolated extra-medullary disease, testicular involvement or bulky disease
• Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome.
• Patients with Burkitt's lymphoma/leukemia
• History of active neurological auto immune or inflammatory disorders

Other protocol-defined inclusion/exclusion criteria may apply.