VOB560-MIK665 Combination First in Human Trial in Patients With Hematological Malignancies (Relapsed/Refractory Non-Hodgkin Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia, or Relapsed/Refractory Multiple Myeloma)

A Phase Ib, Multicenter Study of VOB560 in Combination With MIK665 in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia, or Relapsed/Refractory Multiple Myeloma.

ClinicalTrials.gov Identifier: NCT04702425

Novartis Reference Number: CVOB560A12101

Last Update: Mar 21, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of the study is to identify doses and schedules of VOB560 and MIK665 that can be safely given and to learn if the combination can have possible benefits for patients with Non-Hodgkin lymphoma (NHL), Multiple Myeloma (MM) or Acute Myeloid Leukemia (AML).

VOB560 and MIK665 are selective and potent blockers respectively of the B-cell lymphoma 2 (BCL2) protein and of the myeloid cell leukaemia 1 (MCL1) protein, proteins that may protect tumor cells from undergoing cell death. VOB560 and MIK665 are designed to block the functions of the BCL2 and MCL1 proteins, so that the tumor cells that rely on these proteins undergo cell death.

Preclinical data suggest that concomitant treatment with VOB560 in combination with MIK665 induces robust anti-tumor activity.

Condition 
Non-Hodgkin Lymphoma (NHL)
Acute Myeloid Leukemia (AML)
Multiple Myeloma (MM)
Phase 
Phase 1
Overall status 
Recruiting
Start date 
Jun 23, 2021
Completion date 
Jan 02, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
VOB560
Powder for concentrate for solution for infusion
Drug
MIK665
Concentrate for solution for infusion

Eligibility Criteria

Inclusion Criteria:

Diagnosis of one of the following hematologic malignancies:

relapsed and/or refractory patients with non-Hodgkin lymphoma with radiographically measurable disease with a clearly demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extra nodal lesion at least 1.0 cm in its largest dimension
relapsed and/or refractory patients with MM treated with at least 2 prior regimens, including an IMiD, a proteasome inhibitor proteasome inhibitor, and anti-CD38 antibody (if available) and not eligible for treatment with other regimens known to provide clinical benefit, as determined by the investigator.
relapsed and/or refractory patients with Acute Myeloid Leukemia (AML), pathologically confirmed diagnosis as defined by the WHO Classification and with ≥ 5% blasts in bone marrow. Following ≥ 1 prior therapies who have relapsed or exhibited refractory disease (primary failure) and are deemed by the investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established therapeutic regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded).
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institution's 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.

Exclusion Criteria:

History of severe hypersensitivity reactions to any ingredient of study treatment and/or their excipients.
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 shorter, before the first dose of study treatment.
High-risk patients for Tumor Lysis Syndrome according to Cairo et al 2010 criteria or local guidelines.

Impaired cardiac function or clinically significant cardiac disease, or history or current diagnosis of ECG abnormalities indicating significant risk of safety including any of the following:

Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker
Any history of clinical important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, significant hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment
Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study.
Abnormal echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) at baseline (left ventricular ejection fraction [LVEF] <50%)
Symptomatic congestive heart failure (New York Heart Association ≥ 3)
Findings observed in the baseline cardiac MRI that might reflect an increased risk for cardiac adverse events.
Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior to start of study treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained.
For AML patients: Peripheral blast counts > 25,000 blasts / mm3. Patients can receive hydroxyurea to control the peripheral blast counts as long as hydroxyurea can be stopped at least 24 hours prior to obtaining PD biomarkers at screening/baseline. Hydroxyurea can be restarted after sampling if clinically indicated to control blasts prior to the start of study treatment markers.

For patients with R/R NHL and R/R MM:

Absolute Neutrophil count < 1.0 x 109/L
Platelets count < 50 x 109/ L
Hemoglobin < 8 g/dl
Autologous stem cell transplant within 3 months before the first dose of study treatment.
Patients who have undergone a prior allogeneic stem cell transplant before the first dose of study treatment.
History of or current interstitial lung disease or pneumonitis grade ≥ 2.

Impaired hepatic and renal function defined as:

Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN)
Bilirubin >1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
Creatinine clearance <50 mL/min (calculated using Cockroft-Gault formula, or measured).
Lipase >1.5 x ULN or serum amylase >1.5 x ULN and no history of pancreatitis.
Increased cardiac troponin above the manufacturer's 99th percentile upper reference limit for local assay at screening

Other protocol-defined inclusion/exclusion criteria may apply

Study Locations

Belgium
Novartis Investigative Site
Recruiting
Gent, 9000
-
Belgium
Finland
Novartis Investigative Site
Recruiting
HUS, FIN-00029
-
Finland
Germany
Novartis Investigative Site
Recruiting
Heidelberg, 69120
-
Germany
Hong Kong
Novartis Investigative Site
Recruiting
Hong Kong,
-
Hong Kong
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
Recruiting
Rozzano, 20089
MI
Italy
Japan
Novartis Investigative Site
Recruiting
Sunto Gun, 411 8777
Shizuoka
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Spain
Novartis Investigative Site
Recruiting
Santander, 39008
Cantabria
Spain
Novartis Investigative Site
Recruiting
Salamanca, 37007
Castilla Y Leon
Spain

Contacts

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Phone: 
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