VOB560 + MIK665 for Blood Cancer

Recruiting at 14 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

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two new drugs, VOB560 and MIK665, on patients with certain blood cancers. These drugs aim to block proteins that help cancer cells survive, making it easier for the body to eliminate them.

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.

What data supports the effectiveness of the drug combination VOB560 + MIK665 for blood cancer?

Research shows that combining inhibitors targeting PIM and Akt pathways, similar to VOB560 and MIK665, can effectively reduce leukemia cell survival by affecting key survival pathways in acute myeloid leukemia (AML). This suggests potential effectiveness for blood cancer treatment. ^{1 2 3 4 5}

What makes the drug VOB560 + MIK665 unique for treating blood cancer?

The combination of VOB560 and MIK665 is unique because it targets specific pathways involved in blood cancer cell survival, potentially offering a novel approach compared to existing treatments. While the exact mechanisms of VOB560 are not detailed, similar treatments like Tomivosertib target MNK1/2 pathways, which are crucial in leukemia, suggesting that VOB560 may have a similar innovative mechanism. ^{2 4 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Insights in dynamic kinome reprogramming as a consequence of MEK inhibition in MLL-rearranged AML. [2021]

2. England pubmed.ncbi.nlm.nih.gov

PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Dual targeting of acute myeloid leukemia progenitors by catalytic mTOR inhibition and blockade of the p110α subunit of PI3 kinase. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Inhibitory effects of Tomivosertib in acute myeloid leukemia. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior antileukemic activity against AML ex vivo. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia. [2021]