Phase I Trial of Vididencel in CML-CP Patients With MRD Under TKI Treatment

An Open-Label, Single-Arm Phase 1 Trial to Evaluate the Safety, Tolerability and Efficacy of Vididencel in Chronic Phase Chronic Myeloid Leukemia Patients With Measurable Residual Disease Unable to Meet Requirements of Treatment Free Remission Under Tyrosine Kinase Inhibitor Treatment

The main purpose of the trial is to evaluate the safety and potential side effects of cell therapy vididencel in Chronic Myeloid Leukemia (CML) participants with measurable residual disease (MRD) unable to stop treatment with tyrosine kinase inhibitor (TKI). Patients may not receive any direct medical benefit from participating. Participants in the study should have been treated with TKI for at least 24 months prior to enrolment. This TKI must be of the same type throughout the 24 months. Participation in the active period of the study will take about 5 months after which patients will be followed with regular checks for a total of 3 years from the study start. The cell therapy is administered as 2 low-volume intradermal injections.The first 4 treatments will be performed once every two weeks over a period of 6 weeks. Further treatments are given 14 and 18 weeks after the start of participation as 1 low-volume intradermal injection.The belief is that addition of the study treatment (vididencel) to tyrosine kinase inhibitor therapy may potentially strengthen the immune defence so that enough leukemic cells are killed that the TKI treatment can eventually be decreased in dose or even stopped permanently, without the CML progressing again.

Inclusion Criteria:

• Male or female aged ≥ 18 years at the time of informed consent.

Signed and dated informed consent document indicating that the participant has been informed of all the pertinent aspects of the trial prior to any study-related activities.

Willing to comply with clinical trial instructions and requirements.

Confirmed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) (according to ELN 2025) treated with the same TKI for minimum 24 months.

MRD positive meaning BCR::ABL1 <10% - >0.01% IS at a stable level over the last 6 months. A value must not increase to ≥ 3 fold from baseline or a value must not decrease to ≤ 1/3 fold from baseline. All three measurements must fall within a 3-fold range, i.e., the ratio between the highest and lowest of the three values must be <3.

Adequate performance status: Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Expected co-operation of participant regarding treatment and follow-up procedures according to the treating physician.

Women of childbearing potential (WOCBP) defined as all women physiologically capable of becoming pregnant, must present a negative serum pregnancy test result within 3 days prior to first dosing and a negative urine pregnancy test on the day of first dosing. Additionally,they must use a highly effectiveform of contraception (with Pearl index < 1%) throughout the study and for at least 3 months after the last dose of study medication.

Men with partners of childbearing potential must be willing to use condoms during intercourse while on study and should not father a child in this period. A condom is required to be used also by vasectomized men

Exclusion Criteria:

• Participants who are scheduled for allogeneic stem cell transplantation (allo HSCT) or participants who have undergone allo HSCT less than 5 years ago. Participants who have undergone allo HSCT more than 5 years ago and had any sign of graft-versus-host disease.

Uncontrolled or serious infections.

Ongoing systemic immunosuppressive therapy, other than short use of low dose steroids, i.e. equivalent to an average dose of ≤10 mg of prednisone/day.

Use of any other experimental drug or therapy within 28 days or 5 half-lives of the investigational drug, whichever is longer of baseline.

Active autoimmune disease or participants with recent history, except for well controlled diabetes and stable thyroid disease.

Inadequate liver function (AST and ALT > 3 x upper limit of normal (ULN), serum bilirubin >3 x ULN).

Other active malignancies within the last 5 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma carcinoma of the skin.

Pregnant or lactating females.

Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment.

Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned treatment, affect participant compliance or place the participant at high risk from treatment-related complications.

Known HIV, Hepatitis B and/or Hepatitis C infections.

Known hypersensitivity to vididencel, or any of the ingredients or excipient in the formulation.

Participants who, in the opinion of the Investigator, would clinically benefit from switching to an alternative TKI therapy