Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS

Novartis

Status and phase: Terminated; Phase 1

Conditions: Myelodysplastic Syndromes

Treatments: Drug: MBG453; Drug: canakinumab; Drug: NIS793

Study type: Interventional

Funder types: Industry

Identifiers

NCT04810611

2019-004623-21 (EudraCT Number)

CMBG453E12101

Details and patient eligibility

About

The purpose of this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.

Full description

This was a phase Ib, multi center, open-label, platform study with multiple treatment arms.

The design of this study was adaptive to allow discontinuation of poorly tolerated or ineffective treatments and to facilitate the introduction of new candidate single agents or combinations. Study design included a dose escalation/confirmation part and a dose expansion.

The planned initial single agent and combination treatment arms were the following:

• Arm 1: MBG453 single agent
• Arm 2: NIS793 single agent
• Arm 3: canakinumab single agent
• Arm 4: MBG453 + NIS793 combination
• Arm 5: MBG453 + canakinumab combination Patients were treated in the dose confirmation/escalation part of the study in Arms 1, 2, 3 and 5. No patients were treated in Arm 4. The study did not progress into the expansion phase.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF).

3. Patients must have a diagnosis prior to participation in the study of IPSS-R very low, low, or intermediate risk MDS with ≤10% bone marrow blasts and one or more of the following:

   1. Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)
   2. Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level ≥ 500 /uL
   3. Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL
   4. Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)

4. Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

6. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions' guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study -

Key Exclusion Criteria:

1. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
3. Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
4. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or ESAs anytime ≤ 2 weeks (or 5 half-lives, whichever is longer) prior to start of study treatment.
5. Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
6. For arms containing canakinumab: Patients with ANC < 500 /µL

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

33 participants in 5 patient groups

Arm 1: MBG453 single agent

Experimental group

Description:

Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.

Treatment:

Drug: MBG453

Arm 2: NIS793 single agent

Experimental group

Description:

Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.

Treatment:

Drug: NIS793

Arm 3: canakinumab single agent

Experimental group

Description:

Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.

Treatment:

Drug: canakinumab

Arm 4: MBG453 + NIS793 combination

Experimental group

Description:

Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.

Treatment:

Drug: NIS793

Drug: MBG453

Arm 5: MBG453 + canakinumab combination

Experimental group

Description:

Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.

Treatment:

Drug: canakinumab

Drug: MBG453