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Myelodysplastic SyndromesPhase 1/2NCT05367401

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

A Phase 1/2 study testing Sabatolimab, Magrolimab and Azacitidine in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sabatolimab, Magrolimab and Azacitidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
20 Dec 2024to 26 Oct 2029
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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.
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  • 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)
  • Other protocol defined inclusion/exclusion criteria may apply

About this study

Official title: A Phase Ib/II, Open Label, Proof-of-concept Study of Sabatolimab and Magrolimab-based Therapy for Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

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.

Read the detailed description

The primary purpose of the Safety run-in is to rule out excessive toxicity and investigate safety of the combination of sabatolimab with azacitidine and magrolimab in previously untreated participants with higher-risk MDS and unfit AML. The primary purpose of the combined Safety Run-in and Expansion is to assess the preliminary efficacy of the combination of sabatolimab with magrolimab with (cohort 1 and 2) or without (cohort 3) azacitidine in terms of achieving complete remission in 3 different indications:

  • Previously untreated participants with AML, who are unfit for intensive chemotherapy (1L unfit AML - cohort 1),
  • Previously untreated participants with higher-risk MDS (1L higher risk MDS - cohort 2),
  • Participants with R/R AML after having been previously treated with only first line venetoclax in combination with hypomethylating agent (VEN+HMA) (R/R AML - cohort 3).
Being tested
Sabatolimab, Magrolimab, Azacitidine
Keywords
relapsed/refractory, R/R, Phase 1/2, Sabatolimab, Magrolimab, Azacitidine, Myelodysplastic Syndromes, MDS, Acute myeloid leukemia, AML, TIM-3, CD47
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SabatolimabDrug

    Also called MBG453

    Solution for intravenous infusion

  • MagrolimabDrug

    Also called GS-4721

    Solution for intravenous infusion

  • AzacitidineDrug

    Solution for subcutaneous injection or intravenous infusion

Study groups in NCT05367401
Study groupRoleWhat they receive
1L higher risk MDSExperimentalParticipants with 1L MDS will receive sabatolimab and magrolimab in combination with azacitidine
Receives: Drug: Sabatolimab; Drug: Magrolimab; Drug: Azacitidine
1L unfit AMLExperimentalParticipants with 1L AML unfit for intensive chemotherapy will receive sabatolimab and magrolimab in combination with azacitidine
Receives: Drug: Sabatolimab; Drug: Magrolimab; Drug: Azacitidine
Relapsed/refractory AML previously treated with venetoclax and azacitidineExperimentalParticipant 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)
Receives: Drug: Sabatolimab; Drug: Magrolimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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.

    Measured: Up to 4 years from last patient first treatment

Secondary outcomes (14)

  1. Anti-drug-antibody prevalence at baseline

    Measuring immunogenicity to sabatolimab and magrolimab prior to exposure

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

  2. Anti-drug-antibody prevalence on treatment

    Measuring immunogenicity to sabatolimab and magrolimab on treatment and after treatment

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

  3. Peak of Serum Concentration (Cmax) sabatolimab and magrolimab

    Maximal serum concentration of sabatolimab and magrolimab

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

  4. Trough serum concentration (Cmin) sabatolimab

    Concentration of sabatolimab prior to next dosing or after end of treatment

    Measured: 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

  5. Trough serum concentration (Cmin) magrolimab

    Concentration of magrolimab prior to next dosing or after end of treatment

    Measured: 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

  6. Time from first occurrence of CR (complete remission) to relapse from CR or death due to any cause whichever occurs first (All 3 arms)

    Assessing the duration of complete response defined as time from first occurence of CR per IWG -Cheson 2003) and ELN Doehner 2017 AML recommendations (AML) and per modified IWG-MDS criteria (MDS) to relapse from CR per IWG CHeson 2003 and ELN -Doehner 2017 AML recommendations (AML) and per modified IWG-MDS criteria Cheson 2006 (MDS) or death due to any cause ,whichever occurs first

    Measured: Up to 4 years from last patient first treatment

  7. Percentage of participants achieving CR, CR with incomplete hematologic recovery (CRi), or partial response (PR) as per Investigator (1L unfit AML and R/R AML arms only)

    Assessing the overall response rate defined as proportion of participants achieving CR, CR with incomplete hematologic recovery (CRi), or partial response (PR) as per investigator assessment as per ELN -Doehner 2017 and IWG criteria -Cheson 2003

    Measured: Up to 4 years from last patient first treatment

  8. Percentage of participants achieving CR or CRi (1L unfit AML and R/R AML arms only)

    Assessing the [CR + CRi] rate defined as proportion of patients achieving complete remission or complete remission with incomplete hematologic recovery per IWG - Cheson 2003 and ELN AML recommendations -Doehner 2017 (AML)

    Measured: Up to 4 years from last patient first treatment

  9. Percentage of participants achieving CR or CRh (1L unfit AML and R/R AML arms only)

    Assessing the [CR + CR with partial hematologic recovery (CRh)] rate defined as proportion of patients achieving complete remission or complete remission with partial hematological recovery per IWG and ELN AML recommendations (AML)

    Measured: Up to 4 years from last patient first treatment

  10. Percentage of participants achieving CR with Measurable Residual Disease (MRD)-negative status(1L unfit AML and R/R AML arms only)

    Assessing the rate of MRD-negative CR participants defined as proportion of participants in complete remission with no detectable minimal residual disease

    Measured: Up to Day 1 of cycle 13 ; Cycle=28 days

  11. Percentage of participants achieving CR or CRi with MRD-negative status (1L unfit AML and R/R AML arms only)

    Rate of MRD-negative participants Assessing the rate of MRD-negative CR /CRi participants defined as proportion of participants in either complete remission or complete remission with incomplete hematologic recovery with no detectable minimal residual disease

    Measured: Up to Day 1 of Cycle 13 ; Cycle =28 days

  12. Percentage of participants achieving CR, marrow CR (mCR), partial response (PR), hematologic improvement (HI) per Investigator assessment (1L higher risk MDS arm only)

    Assessing the overall response rate defined as proportion of patients achieving CR, marrow CR (mCR), partial response (PR), hematologic improvement (HI) per Investigator assessment according to modified IWG-MDS response criteria- Cheson 2006

    Measured: Up to 4 years from last patient first treatment

  13. Percentage of participants who are red blood cells (RBC)/platelets transfusion independent (1L MDS arm only)

    Assessing the improvement in RBC/platelets transfusion independence

    Measured: From start of treatment up to until 4 years after last patient first treatment

  14. Duration of transfusion independence (1L MDS arm only)

    Assessing the time to RBC/platelets transfusion independence

    Measured: From start of treatment up to until 4 years after last patient first treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2022
  2. Study start20 Dec 2024 (estimated)
  3. Primary completion26 Oct 2029 (estimated)
  4. Study completion26 Oct 2029 (estimated)

Why it stopped: waiting for update from Study Lead

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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)
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05367401
Sponsor's protocol ID
CMBG453B12205
Other IDs
2021-003263-10
Status last verified
Apr 2024
First submitted
21 Apr 2022
Last updated
11 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The Trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sabatolimab, Magrolimab and Azacitidine in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Novartis Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of participants with dose limiting toxicities (only for participants enrolled in the safety run-in part) (time frame: Cycle 1 Day 1 to the end of Cycle 2 (up to 14 days from the planned cycle 3 Day 1) ; Cycle = 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05367401.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2024.

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