A Study of Sabatolimab and Magrolimab-based Treatment in AML or Higher Risk MDS Participants

NCT05367401 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: CMBG453B122052021-003263-10
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is to determine the safety and preliminary efficacy of sabatolimab in combination with magrolimab and azacitidine in adult participants with 1L unfit Acute Myeloid Leukemia (AML) or with 1L higher risk Myelodysplastic Syndromes (MDS), and sabatolimab in combination with magrolimab in participants with relapsed or refractory (R/R) AML.

Conditions

Myelodysplastic Syndromes; Acute Myeloid Leukemia

Keywords

relapsed/refractory; R/R; Phase 1/2; Sabatolimab; Magrolimab; Azacitidine; Myelodysplastic Syndromes; MDS; Acute myeloid leukemia; AML; TIM-3; CD47

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with dose limiting toxicities (only for participants enrolled in the safety run-in part)

  Assessment of tolerability of sabatolimab and magrolimab given together with azacitidine

  Cycle 1 Day 1 to the end of Cycle 2 (up to 14 days from the planned cycle 3 Day 1) ; Cycle = 28 Days

• Percentage of participants achieving complete remission (CR) according to Investigator assessment per treatment arm

  Assessing the Complete Remission (CR) Rate in each treatment arm (including participants from safety run-in and expansion) per IWG -Cheson 2003 and ELN AML recommendations - Doehner 2017 (AML) and per modified IWG-MDS criteria- Cheson 2006 (MDS) in each treatment arm.

  Up to 4 years from last patient first treatment

Secondary Outcomes (14)

• Anti-drug-antibody prevalence at baseline

  prior to first dose of sabatolimab on week 2 Day 1 and first dose of magrolimab on week 1 day 1

• Anti-drug-antibody prevalence on treatment

  Throughout study until 90 day safety follow up for sabatolimab and 30 day safety follow up for magrolimab

• Peak of Serum Concentration (Cmax) sabatolimab and magrolimab

  Day 1 of week 2, 5, 13 for sabatolimab. Day 1 or week 1, 5, 13 for magrolimab

• Trough serum concentration (Cmin) sabatolimab

  Day 1 of week 2, 5, 9, 13, 25, 37, 49, 73, 97, end of treatment (EOT) (within 7 days after the last dose of study treatment), 30 days after last dose of sabatolimab, and 90 days after the last dose of sabatolimab for sabatolimab

• Trough serum concentration (Cmin) magrolimab

  Day 1 or week 1, 2, 5, 9, 13, 25, 37, 49, 73, 97, end of treatment (EOT) (within 7 days after the last dose of study treatment), 30 days after last dose of magrolimab for magrolimab

Study Arms (3)

1L higher risk MDS

EXPERIMENTAL

Participants with 1L MDS will receive sabatolimab and magrolimab in combination with azacitidine

Drug: Sabatolimab; Drug: Magrolimab; Drug: Azacitidine

1L unfit AML

EXPERIMENTAL

Participants with 1L AML unfit for intensive chemotherapy will receive sabatolimab and magrolimab in combination with azacitidine

Drug: Sabatolimab; Drug: Magrolimab; Drug: Azacitidine

Relapsed/refractory AML previously treated with venetoclax and azacitidine

EXPERIMENTAL

Participant with relapsed/refractory AML will receive sabatolimab and magrolimab (in absence of complete response (CR), Complete Remission with incomplete hematologic recovery (CRi) or Morphologic Leukemia-Free State (MLFS) after 2 cycles, participants will be allowed to also receive azacitidine)

Drug: Sabatolimab; Drug: Magrolimab

Interventions

Sabatolimab DRUG

Solution for intravenous infusion

Also known as: MBG453

1L higher risk MDS; 1L unfit AML; Relapsed/refractory AML previously treated with venetoclax and azacitidine

Magrolimab DRUG

Solution for intravenous infusion

Also known as: GS-4721

1L higher risk MDS; 1L unfit AML; Relapsed/refractory AML previously treated with venetoclax and azacitidine

Azacitidine DRUG

Solution for subcutaneous injection or intravenous infusion

1L higher risk MDS; 1L unfit AML

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Age ≥ 18 years at the date of signing the informed consent form (ICF)
• Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or 3, or any of the following comorbidities: severe cardiac comorbidity (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin \>1.5 to 3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m\^2 to 45 30 ml/min/1.73m\^2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessment and approved by the Novartis Medical monitor) OR
• Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016), that is intermediate, high or very high risk (higher risk) based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012), previously untreated for higher risk MDS \[1L higher risk MDS\]:
• Intermediate (\>3-4.5 points)
• High (\> 4.5-6 points)
• Very high (\> 6 points) OR (for expansion only) Participants with AML relapsed or refractory to venetoclax in combination with a hypomethylating agent (VEN+HMA) as defined by failure to achieve bone marrow blast \<5% after at least 2 cycles of VEN+HMA (refractory) or relapsed after having achieved BM blast \<5% following previous treatment with VEN+HMA as first and the only line of treatment for AML
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0-2 for participants ≥ 75 years of age, OR 0-3 for participants \< 75 years of age
• White blood cell (WBC) count ≤ 20 x 10\^3/μL prior to first dose of study treatment (may be reduced with leukapheresis, hydroxyurea, or oral etoposide)
• Hemoglobin ≥ 9 g/dL prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility prior to first dose of study treatment

You may not qualify if:

• Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents
• Prior exposure to TIM-3 directed therapy
• Prior therapy with immune checkpoint inhibitors (eg, anti-CTLA4, anti-PD-1, anti-PDL1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of the study treatment
• For participants with higher risk MDS only: Previous first-line treatment for intermediate, high, very high risk (higher risk) MDS (based on IPSS-R) with any antineoplastic agents including for example chemotherapy and hypomethylating agents such as decitabine or azacitidine.
• For participants with newly diagnosed AML only: Previous treatment at any time, with any approved or investigational antineoplastic agents for AML or higher risk MDS.
• Prior and concurrent therapy with hydroxyurea or oral etoposide (to reduce WBC count), supportive care ruxolitinib, erythroid and/or myeloid growth factors are allowed.
• Acute promyelocytic leukemia
• Known inherited or acquired bleeding disorders
• Patients with CNS leukemia or neurologic signs and symptoms suggestive of CNS leukemia (unless CNS leukemia had been excluded)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Recurrence

Interventions

sabatolimab; magrolimab; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Safety run in (1L higher risk MDS + 1L unfit AML) followed by parallel expansion cohorts (1L higher risk MDS, 1L unfit AML, relapsed/refractory AML)

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: May 10, 2022
• Study Start: December 20, 2024
• Primary Completion (Estimated): October 26, 2029
• Study Completion (Estimated): October 26, 2029
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share