This is a phase 1, open-label, multicenter, dose-escalation, and cohort expansion study
designed to evaluate the safety, tolerability, PK, and antitumor activity of SEA-CD70 in
adults with myeloid malignancies. The study will be conducted in up to 3 parts.
Part A is a dose escalation cohort designed to identify the MTD or recommended expansion dose
of SEA-CD70 in subjects with relapsed/refractory (HMA-failure) MDS. Part B is an expansion
cohort designed to evaluate the safety and tolerability of SEA-CD70 in subjects with
relapsed/refractory (HMA-failure) MDS. Part C is an expansion cohort designed to evaluate the
safety and tolerability of SEA-CD70 in subjects with relapsed/refractory AML.
Part A Inclusion Criteria
- Participants with cytologically/histologically confirmed myelodysplastic syndrome
(MDS) according to the 2016 World Health Organization (WHO) classification with the
following:
- Measurable disease per WHO MDS with excess blasts criteria as defined either:
- 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood or
- 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood
- MDS that is relapsed or refractory and must not have other therapeutic options
known to provide clinical benefit in MDS available.
- Treatment failure after prior hypomethylating agent (HMA) therapy for MDS,
defined as one of the following:
- Progression (per 2006 International Working Group [IWG] criteria) at any
time after initiation of HMA therapy.
- Lack of response (failure to achieve complete remission [CR], partial
response [PR], or hematologic improvement [HI] per 2006 IWG criteria) after
at least 6 cycles of azacitidine (or equivalent HMA) or 4 cycles of
decitabine (or equivalent HMA).
- Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
- Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to
treatment discontinuation).
- Participants with isolated 5q-/5q- syndrome must have progressed, failed,
relapsed, or not tolerated lenalidomide in addition to HMA.
- Must be off HMA therapy ≥ 2 weeks and must be off any other treatments for MDS for ≥ 4
weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed
before and during the study as clinically indicated
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Part B Inclusion Criteria
- Participants with cytologically/histologically confirmed MDS according to the WHO
classification with the following:
- Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined
either:
- 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood, or
- 10%-19% blasts in the bone marrow or 5%-19% in the peripheral blood
- MDS that is relapsed or refractory and must not have other therapeutic options
known to provide clinical benefit in MDS available.
- Treatment failure after prior HMA therapy for MDS defined as one of the
following:
- Progression (per 2006 IWG criteria) at any time after initiation of HMA
therapy.
- Lack of response (failure to achieve CR, PR, or HI per 2006 IWG criteria)
after at least 6 cycles of azacitidine or 4 cycles of decitabine.
- Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
- Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to
treatment discontinuation).
- Participants with isolated 5q-/5q- syndrome must have progressed, failed,
relapsed, or not tolerated lenalidomide in addition to HMA.
- Must be off HMA therapy ≥ 2 weeks and must be off any other systemic treatments for
MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors (e.g., G-CSF,
erythropoietin and thrombopoietin) and transfusions are allowed before and during the
study as clinically indicated.
- ECOG Performance Status of 0-2
Part C Inclusion Criteria
- Participants with relapsed or refractory acute myeloid leukemia (AML) according to the
WHO 2016 classification (except for acute promyelocytic leukemia [APL]):
- Who have received either 2 or 3 previous regimens to treat active disease.
Post-remission treatments, intrathecal chemotherapy, and radiotherapy are not
considered previous regimens.
- Who have received 1 previous regimen to treat active disease and have at least
one of the following:
- Age > 60 and ≤75 years.
- Primary resistant AML (defined as failure to achieve CR after 1-2 courses of
induction therapy)
- First CR duration <6 months
- Adverse-risk per European Leukemia Net (ELN) genetic risk stratification
- Secondary AML (prior history of MDS or therapy-related)
- Age 18-75 years
- ECOG performance status of 0-2
Exclusion Criteria (All Parts)
- History of another malignancy within 3 years before the first dose of study drug or
any evidence of residual disease from a previously diagnosed malignancy. Exceptions
are malignancies with a negligible risk of metastasis or death.
- Previous exposure to CD70-targeted agents
- Prior allogeneic hematopoietic stem cell transplant, for any condition
- Central nervous system leukemia based on imaging or documented positive cytology in
cerebral spinal fluid
- History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or
idiopathic thrombocytopenic purpura