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Non-Hodgkin Lymphoma (NHL)Phase 1NCT04702425

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 1 study testing VOB560 and MIK665 in people with Non-Hodgkin Lymphoma (NHL) and Acute Myeloid Leukemia (AML), run by Novartis Pharmaceuticals at 9 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of the study was 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
VOB560 and MIK665
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
9 sitesin 9 countries
Study dates
23 Jun 2021to 23 Jul 2024
Phase
Phase 1
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

  • 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.

Who cannot join

  • 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
Show all 28Show fewer
  • 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

Trial locations and contacts

9 sites in 9 countries.

9 sites in 9 countries

United States1 site
  • Uni of TX MD Anderson Cancer Cntr UT MD Anderson Cancer Ctr

    Houston, Texas, 77030

Other trials in United States

Belgium1 site
  • Novartis Investigative Site

    Ghent, 9000

Other trials in Belgium

Finland1 site
  • Novartis Investigative Site

    HUS, FIN-00029

Other trials in Finland

Hong Kong1 site
  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

Israel1 site
  • Novartis Investigative Site

    Tel Aviv, 6423906

Other trials in Israel

Italy1 site
  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Japan1 site
  • Novartis Investigative Site

    Sunto Gun, Shizuoka, 411 8777

Other trials in Japan

South Korea1 site
  • Novartis Investigative Site

    Seoul, 03080

Other trials in South Korea

Spain1 site
  • Novartis Investigative Site

    Santander, Cantabria, 39008

Other trials in Spain

About this study

Official title: 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.

The purpose of the study was 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.

Read the detailed description

This was an open-label, non-randomized multi-center phase Ib dose-escalation study with dose expansion arms in four different patient populations. Patients received VOB560 in combination with MIK665 in a once a week (QW) schedule over 21 days cycle. Less frequent dosing schedules could be explored based on emerging data. Patients were to be treated until disease progression or unacceptable toxicities occurred.

The study included a dose escalation part (Part 1) and a dose expansion part (Part 2).

The following escalation arms were planned:

  • Arm A: relapsed/refractory (R/R) NHL and R/R MM
  • Arm B: R/R AML There were 4 expansion arms planned. However, the expansion part of the study was not initiated.
Being tested
VOB560, MIK665
Keywords
Phase Ib, BHLRM, VOB560, MIK665, NHL, AML, MM, Bcl2, Mcl1
Medical subject headings
Lymphoma, Non-Hodgkin, Leukemia, Myeloid, Acute, Multiple Myeloma

What participants receive

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

  • VOB560Drug

    Also called S65487

    Powder for concentrate for solution for infusion

  • MIK665Drug

    Also called S64315

    Concentrate for solution for infusion

Study groups in NCT04702425
Study groupRoleWhat they receive
VOB560-MIK665 - Part 1aExperimentalPart 1a - Patients with relapsed/refractory non-Hodgkin lymphoma and relapsed/refractory multiple myeloma administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665
VOB560-MIK665 - Part 1bExperimentalPart 1b - Patients with relapsed/refractory acute myeloid leukemia administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665
VOB560-MIK665 - Part 2aExperimentalPart 2a - Patients with relapsed/refractory multiple myeloma with at least 10 patients with 1q gain cytogenetic abnormality and 10 patients with high risk R/R MM as defined in (Sonneveld et al 2016) administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665
VOB560-MIK665 - Part 2bExperimentalPart 2b - Patients with relapsed/refractory non-Hodgkin lymphoma with at least 10 patients with double-hit (DH) lymphoma, based on the overall bad prognosis and limited therapeutic options for patients with DH NHL administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665
VOB560-MIK665 - Part 2cExperimentalPart 2c - Patients with relapsed/refractory acute myeloid leukemia venetoclax refractory or insensitive with at least 6 patients M5 as proposed by French-American-British (FAB) group, based on the observation that venetoclax resistance in AML M5 can be caused by up-regulation of MCL1 administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665
VOB560-MIK665 - Part 2dExperimentalPart 2d - Patients with relapsed/refractory acute myeloid leukemia venetoclax naive patients administered VOB560 and MIK665 as an intravenous (IV) infusion.
Receives: Drug: VOB560; Drug: MIK665

What is being measured

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

  1. Incidence and severity of AEs and SAEs, including changes in lab values, vital signs, and ECGs

    Month 18 is assumed to be study end

    Measured: at month 18

  2. Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment with VOB560 and MIK665 in combination

    Month 18 is assumed to be study end

    Measured: at month 18

  3. Frequency of dose interruptions

    Month 18 is assumed to be study end

    Measured: at month 18

  4. Frequency of dose reductions

    Month 18 is assumed to be study end

    Measured: at month 18

  5. Dose intensities

    Month 18 is assumed to be study end

    Measured: at month 18

Secondary outcomes (15)
  1. Overall Response Rate (ORR)

    Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL

    Measured: at month 18

  2. Complete Response (CR) rate (and rate of CR or sCR in R/R MM)

    Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL

    Measured: at month 18

  3. Best Overall Response (BOR)

    Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL

    Measured: at month 18

  4. Duration Of Response (DOR)

    Month 18 is assumed to be study end Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL

    Measured: at month 18

  5. Progression Free Survival (PFS)

    Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL

    Measured: at month 18

  6. Area Under Curve (AUC) of VOB560

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  7. Maximum Plasma Concentration (Cmax) ok VOB560

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  8. Terminal elimination half-life (T1/2) of VOB560

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  9. Clearance (CL) of VOB560

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  10. Apparent volume of distribution (Vz) of VOB560

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  11. Area Under Curve (AUC) of MIK665

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  12. Maximum Plasma Concentration (Cmax) ok MIK665

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  13. Terminal elimination half-life (T1/2) of MIK665

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  14. Clearance (CL) of MIK665

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

  15. Apparent volume of distribution (Vz) of MIK665

    PK parameter

    Measured: At the end of Cycle 6 (each cycle is 21 days)

Timeline

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

  1. First posted8 Jan 2021
  2. Study start23 Jun 2021
  3. Primary completion23 Jul 2024
  4. Study completion23 Jul 2024

Why it stopped: Business reasons

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04702425
Sponsor's protocol ID
CVOB560A12101
Other IDs
2020-004691-18
Status last verified
Oct 2025
First submitted
2 Dec 2020
Last updated
10 Oct 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VOB560 and MIK665 in people with Non-Hodgkin Lymphoma (NHL) and Acute Myeloid Leukemia (AML), run by Novartis Pharmaceuticals at 9 sites in 9 countries.

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 6 inclusion and 28 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: stopped early, as of the sponsor's last update on 10 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Belgium, Finland, Hong Kong, Israel and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

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 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.

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 stopped early (reason given: Business reasons). Results are not available in the source record.

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?

Incidence and severity of AEs and SAEs, including changes in lab values, vital signs, and ECGs (time frame: at month 18). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 10 Oct 2025.

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