VOB560 + MIK665 for Blood Cancer

No longer recruiting at 16 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: QT prolonging agents

Disqualifiers: Severe cardiac disease, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination to help people with certain blood cancers, such as Non-Hodgkin lymphoma, Multiple Myeloma, or Acute Myeloid Leukemia. The researchers aim to find safe doses and schedules for two drugs, VOB560 and MIK665, which work together to encourage cancer cell death. This trial suits those whose cancers have returned or not responded to previous treatments and who have specific measurable disease features. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic cancer treatments or experimental therapies at least 14 days before starting the study treatment. If you are taking medications that prolong the QT interval, you must stop them for the duration of the study. Other medications may be allowed, but the protocol does not specify all details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that early data on the combination of VOB560 and MIK665 indicates it is generally safe for patients with blood cancers such as Non-Hodgkin lymphoma, Multiple Myeloma, and Acute Myeloid Leukemia. Most patients can tolerate the treatment well. However, these results stem from early research, and further studies are necessary to confirm safety. Participation in trials helps researchers gather more information about the safety and effectiveness of new treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VOB560 and MIK665 because they introduce a new approach to treating blood cancers like non-Hodgkin lymphoma, multiple myeloma, and acute myeloid leukemia. Unlike traditional treatments like chemotherapy and standard immunotherapies, these drugs are administered as intravenous infusions and specifically target pathways that are often resistant to existing treatments. VOB560 and MIK665 work by inhibiting proteins that help cancer cells survive, such as MCL1, which is particularly promising for patients whose cancer has stopped responding to other therapies. This targeted action not only offers hope for more effective outcomes but also potentially reduces the side effects associated with broader treatments.

What evidence suggests that this trial's treatments could be effective for blood cancer?

Research has shown that VOB560 and MIK665 block proteins that help cancer cells survive. These proteins, BCL2 and MCL1, protect cancer cells from dying. By inhibiting these proteins, VOB560 and MIK665 aim to kill cancer cells. Lab tests suggest that this drug combination can effectively fight tumors. Early clinical studies indicate that this treatment is safe for patients, offering hope for those with blood cancers like Non-Hodgkin lymphoma, Multiple Myeloma, and Acute Myeloid Leukemia. Participants in this trial will receive the combination of VOB560 and MIK665 across various treatment phases, targeting different types of relapsed or refractory blood cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with certain blood cancers (Non-Hodgkin lymphoma, Multiple Myeloma, or Acute Myeloid Leukemia) that have come back or didn't respond to treatment. They should be fairly active (ECOG ≤2), have measurable disease, and must have tried multiple treatments already. People can't join if they've had severe heart issues, very low blood counts, serious allergies to study drugs' ingredients, recent other cancer therapies, or are suitable for standard re-induction chemotherapy.

Inclusion Criteria

I am willing and able to undergo multiple bone marrow tests as required.

I have AML that has not responded to at least one treatment and cannot undergo standard therapy.

My multiple myeloma has returned or didn't respond to treatment, and I've tried at least 2 types of treatment including IMiD, a proteasome inhibitor, and anti-CD38 antibody.

Exclusion Criteria

I have or had serious lung inflammation.

Your heart blood test shows elevated levels of troponin.

Your platelet count is less than 50 x 10^9/L.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients received VOB560 in combination with MIK665 in a once a week schedule over 21 days cycle. Less frequent dosing schedules could be explored based on emerging data.

21 days per cycle

Dose Expansion

Dose expansion part with planned arms for different patient populations, although the expansion part was not initiated.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• MIK665
• VOB560

Trial Overview The trial tests a combination of two new drugs: VOB560 and MIK665. These drugs block proteins BCL2 and MCL1 that help cancer cells avoid death. The goal is to find safe doses and see if the drug combo helps patients by causing cancer cells to die off.

How Is the Trial Designed?

Group I: VOB560-MIK665 - Part 2d Experimental Treatment 2 Interventions

Part 2d - Patients with relapsed/refractory acute myeloid leukemia venetoclax naive patients administered VOB560 and MIK665 as an intravenous (IV) infusion.

Group II: VOB560-MIK665 - Part 2c Experimental Treatment 2 Interventions

Part 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.

Group III: VOB560-MIK665 - Part 2b Experimental Treatment 2 Interventions

Part 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.

Group IV: VOB560-MIK665 - Part 2a Experimental Treatment 2 Interventions

Part 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.

Group V: VOB560-MIK665 - Part 1b Experimental Treatment 2 Interventions

Part 1b - Patients with relapsed/refractory acute myeloid leukemia administered VOB560 and MIK665 as an intravenous (IV) infusion.

Group VI: VOB560-MIK665 - Part 1a Experimental Treatment 2 Interventions

Part 1a - Patients with relapsed/refractory non-Hodgkin lymphoma and relapsed/refractory multiple myeloma administered VOB560 and MIK665 as an intravenous (IV) infusion.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

A novel pan-AKT kinase inhibitor, GSK690693, was found to be effective against 55% of 112 tested hematologic cancer cell lines, with particularly high sensitivity in acute lymphoblastic leukemia (89%), non-Hodgkin lymphoma (73%), and Burkitt lymphoma (67%).

GSK690693 selectively inhibited the growth of malignant cells without affecting normal T lymphocytes, and it induced apoptosis in sensitive ALL cell lines, highlighting its potential as a targeted therapy for specific blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines. Levy, DS., Kahana, JA., Kumar, R.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5997/527609/A-First-in-Human-Study-of-VOB560-in-Combination

A First in Human Study of VOB560 in Combination with ... A first in human study of VOB560 in combination with MIK665 in patients with relapsed/refractory non-Hodgkin lymphoma, acute myeloid leukemia, or multiple ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04702425

NCT04702425 | VOB560-MIK665 Combination First in ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124088256

A First in Human Study of VOB560 in Combination with ... Early clinical data of VOB560 in combination with MIK665 reported an acceptable safety profile in patients with hematological malignancies.

4. dana-farber.org dana-farber.org/clinical-trials/21-216

A Phase Ib, Multicenter Study of VOB560 in Combination ... 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 ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01168

VOB560-MIK665 Combination First in Human Trial ... Preclinical data suggest that concomitant treatment with VOB560 in combination with MIK665 induces robust anti-tumor activity. Eligibility Criteria ...

6. researchgate.net researchgate.net/publication/386491123_A_First_in_Human_Study_of_VOB560_in_Combination_with_MIK665_in_Patients_with_RelapsedRefractory_Non-Hodgkin_Lymphoma_Acute_Myeloid_Leukemia_or_Multiple_Myeloma

A First in Human Study of VOB560 in Combination with ... A First in Human Study of VOB560 in Combination with MIK665 in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, ...