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A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies

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Brief Summary

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It will study SEA-CD70 to find out what its side effects are and if it works for AML and MDS. A side effect is anything the drug does besides treating cancer.

This study will have six groups or "parts."

Part A will find out how much SEA-CD70 should be given to patients.
Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients with MDS.
Part C will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients with AML.
Part D will find out how much SEA-CD70 with azacitidine should be given to patients.
Part E will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat patients with MDS or MDS/AML that has not been treated.
Part F will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat patients with MDS or MDS/AML.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

Part A Inclusion Criteria

Participants with cytologically/histologically confirmed 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% 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 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 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 AML according to International Consensus Classification (ICC) 2022 (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 Network genetic risk stratification
  - Secondary AML (prior history of MDS or therapy-related)
Age 18-75 years
ECOG performance status of 0-2

Parts D and F Inclusion Criteria

Participants with diagnosis of MDS or MDS/AML according to ICC 2022 criteria
Disease which has relapsed, failed to respond after minimum of 6 cycles, or progressed following an HMA in the immediately preceding line of therapy.
Eligible for continued therapy with azacitidine
Must be off any other systemic treatment for AML/MDS. Must be off HMA therapy ≥ (greater than or equal to) 2 weeks and any other systemic treatments for MDS for ≥ (greater than or equal to) 4 weeks prior to first dose of SEA-CD70
ECOG Performance Status 0-2

Parts D and E Inclusion Criteria

Participants with diagnosis of MDS or MDS/AML according to ICC 2022 criteria, previously untreated.
- Participants with MDS/AML should not have AML-defining cytogenetics.
Participants with higher-risk (Moderate High, High, or Very High) per Molecular International Prognostic Scoring System (IPSS-M) MDS and MDS/AML
ECOG Performance Status 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
Parts D and F only: Prior oral HMA or oral HMA-combinations

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