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

Seagen, a wholly owned subsidiary of Pfizer

Status and phase: Enrolling; Phase 1

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia

Treatments: Drug: SEA-CD70; Drug: azacitidine; Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT04227847

SGNS70-101

C5781001 (Other Identifier)

2023-506945-42-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

This is a phase 1, open-label, multicenter, dose-finding, and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SEA-CD70 monotherapy and SEA-CD70 in combination with azacitidine in adults with myeloid malignancies. The study will be conducted in up to 6 parts.

• Part A is a dose-escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 monotherapy in participants with relapsed/refractory (hypomethylating agent [HMA]-failure) MDS.
• Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory (HMA-failure) MDS.
• Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory AML.
• Part D contains dose-finding/dose optimization cohorts designed to evaluate the safety/tolerability and identify the recommended expansion dose of SEA-CD70 in combination with azacitidine in participants with 1) relapsed/refractory (HMA-failure) MDS or MDS/AML, and 2) previously untreated higher-risk per IPSS-M (Moderate High, High or Very High) MDS or MDS/AML.
• Part E is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with previously untreated higher-risk per IPSS-M (Moderate High, High, or Very High) MDS or MDS/AML.
• Part F is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with relapsed/refractory (HMA-failure) MDS or MDS/AML.
• Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with previously untreated AML who are unfit for standard of care induction chemotherapy

Enrollment: 178 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Part A Inclusion Criteria

• 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

Part B Inclusion Criteria

• 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

Part C Inclusion Criteria

• 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

Parts D and F Inclusion Criteria

• 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

Parts D and E Inclusion Criteria

• 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

Part G Inclusion Criteria

• 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.

Exclusion Criteria (All Parts)

• Previous exposure to CD70-targeted agents
• Prior allogeneic hematopoietic stem cell transplant, for any condition
• Central nervous system leukemia
• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
• Parts D, F and G only: Prior oral HMA or oral HMA-combinations
• Part G: conditions that preclude enteral route of administration; concomitant use of strong/moderate CYP3A inducers; history of myeloproliferative neoplasm

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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178 participants in 7 patient groups

Part A

Experimental group

Description:

SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS

Treatment:

Drug: SEA-CD70

Part B

Experimental group

Description:

SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS

Treatment:

Drug: SEA-CD70

Part C

Experimental group

Description:

SEA-CD70 expansion cohort in relapsed/refractory AML

Treatment:

Drug: SEA-CD70

Part D

Experimental group

Description:

SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML

Treatment:

Drug: azacitidine

Drug: SEA-CD70

Part E

Experimental group

Description:

SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML

Treatment:

Drug: azacitidine

Drug: SEA-CD70

Part F

Experimental group

Description:

SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML

Treatment:

Drug: azacitidine

Drug: SEA-CD70

Part G

Experimental group

Description:

SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML

Treatment:

Drug: Venetoclax

Drug: azacitidine

Drug: SEA-CD70