A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Description

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 Pa

Trial Eligibility

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

Study Info

Interventions

Locations Recruiting

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