A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for participants 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 seven groups or parts. * Part A will find out how much SEA-CD70 should be given to participants * Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat participants 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 participants with AML. * Part D will find out how much SEA-CD70 with azacitidine should be given to participants * 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 participants 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 participants with MDS or MDS/AML. * Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with AML. Also, to evaluate safety and tolerability of PF-08046040 in combination with azacitidine and venetoclax in participants with previously untreated AML who are unfit for standard induction chemotherapy.
• Participants with cytologically/histologically confirmed MDS (2016 World Health Organization (WHO) classification) with
‣ Measurable disease per WHO MDS with excess blasts criteria
⁃ MDS that is relapsed or refractory and must not have other therapeutic options
⁃ Treatment failure after prior hypomethylating agent (HMA) therapy for MDS
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Participants with cytologically/histologically confirmed MDS (WHO classification) with:
‣ Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria
⁃ MDS that is relapsed or refractory and must not have other therapeutic options
⁃ Treatment failure after prior HMA therapy for MDS
• ECOG Performance Status of 0-2
• Participants with relapsed or refractory AML (ICC 2022) (except for acute promyelocytic leukemia \[APL\]):
‣ Who have received either 2 or 3 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 or secondary AML
∙ First CR duration \<6 months
∙ Adverse-risk per European Leukemia Network genetic risk stratification
• Age 18-75 years
• ECOG performance status of 0-2
• Participants with diagnosis of MDS or MDS/AML (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
• ECOG Performance Status 0-2
• Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria), previously untreated.
• Participants with higher-risk per IPSS-M MDS and MDS/AML
• ECOG Performance Status 0-2
• Participants with diagnosis of AML (ICC 2022 criteria), previously untreated and ineligible for standard induction chemotherapy.
• Age ≥18 years.
• ECOG Performance Status of 0-2.