FT538 in Subjects With Advanced Hematologic Malignancies

This is a Phase I dose-finding study of FT538 as monotherapy in acute myeloid leukemia (AML) and in combination with monoclonal antibodies in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.


Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of one of the following by treatment regimen:

   * Regimen A (FT538 monotherapy in r/r AML)

     * Primary refractory AML, or
     * Relapsed AML, defined as not in CR after one or more re-induction attempts; if \>60 years of age, prior re-induction therapy is not required
   * Regimens B or C (FT538 + mAb in r/r MM)

     * Regimen B only: MM that has relapsed or progressed after at least two lines of therapies, including a proteasome inhibitor and an immunomodulatory drug
     * Regimen C only: MM that has relapsed or progressed after proteasome inhibitor therapy, and immunomodulatory therapy
     * Regimen B and Regimen C: Measurable disease as defined in the protocol
2. Capable of giving signed informed consent
3. Agreement to comply with study procedures as described in the Schedule of Activities
4. Agrees to contraceptive use as described in the protocol

Exclusion Criteria:

1. Females who are pregnant or breastfeeding
2. ECOG Performance Status ≥ 2
3. Evidence of insufficient hematologic function as defined in the protocol
4. Evidence of insufficient organ function defined as defined by the protocol
5. Clinically significant cardiovascular disease as defined by the protocol
6. Known active central nervous system (CNS) involvement by malignancy
7. Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
8. Currently receiving or likely to require systemic immunosuppressive therapy for any reason during the treatment period
9. Clinically significant infections including HIV, HBV and HCV
10. Live vaccine \<6 weeks prior to start of lympho-conditioning
11. Receipt of an allograft organ transplant
12. Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy
13. Known allergy to albumin (human) or DMSO
14. Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject
15. Any medical condition or clinical laboratory abnormality that per investigator or Medical Monitor judgement precludes safe participation in and completion of the study, or which could affect compliance with protocol conduct or interpretation of results

    Exclusion Criteria Specific to Regimen A (r/r AML)
16. Diagnosis of promyelocytic leukemia with t(15;17) translocation
17. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1

    Exclusion Criteria Specific to Regimens B and C (r/r MM)
18. Plasma cell leukemia defined as a plasma cell count \>2000/mm3
19. Leptomeningeal involvement of MM
20. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the first dose of mAb
21. Allergy or hypersensitivity to antibodies or antibody-related proteins