Tasquinimod for Multiple Myeloma

Overseen By Dan Vogl, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Cytotoxic chemotherapy, Proteasome inhibitors

Disqualifiers: Active malignancy, Cardiovascular condition, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is the first study of tasquinimod, an inhibitor of S100A9, in patients with multiple myeloma.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot have certain treatments like cytotoxic chemotherapy, proteasome inhibitors, Imids, monoclonal antibodies, or systemic corticosteroids shortly before starting the trial. You also cannot take drugs that are strong inhibitors or inducers of CYP3A4 or CYP1A2, or drugs with a narrow therapeutic range metabolized by these enzymes. Check with the trial team for specific guidance on your medications.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study. You must stop cytotoxic chemotherapy 3 weeks before, proteasome inhibitors, Imids, or monoclonal antibodies 2 weeks before, and systemic corticosteroids 7 days before the study. If you are on medications that affect CYP3A4 or CYP1A2 enzymes, you may need to stop those as well.

What data supports the idea that Tasquinimod for Multiple Myeloma is an effective drug?

The available research does not provide specific data supporting the effectiveness of Tasquinimod for Multiple Myeloma. Instead, the studies focus on its use in treating prostate cancer, where it shows promise in slowing disease progression and inhibiting metastasis. For Multiple Myeloma, other drugs like immunomodulatory agents and proteasome inhibitors are highlighted as effective treatments, showing improved response rates and prolonged responses. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tasquinimod for treating multiple myeloma?

Tasquinimod has shown promise in treating prostate cancer by slowing disease progression and inhibiting metastasis (spread of cancer), which suggests it might have potential in treating other cancers like multiple myeloma. Its effects on the immune system and blood vessel growth in tumors could be beneficial in managing multiple myeloma. ^{1 2 3 4 5}

What safety data exists for Tasquinimod in treating multiple myeloma?

The provided research does not contain specific safety data for Tasquinimod in the treatment of multiple myeloma. The only mention of Tasquinimod is in a study related to castration-resistant prostate cancer, where it showed promising effects in inhibiting metastasis and delaying disease progression. No safety data for Tasquinimod in multiple myeloma is available in the given research. ^{1 6 7 8 9}

What is known about the safety of Tasquinimod in humans?

Tasquinimod has been tested in a phase II clinical trial for prostate cancer, showing potential benefits in slowing disease progression, but specific safety data from this trial is not detailed in the available research. ^{1 6 7 8 9}

Is the drug Tasquinimod a promising treatment for Multiple Myeloma?

Yes, Tasquinimod is a promising treatment for Multiple Myeloma. It works by targeting and reducing the activity of certain immune cells that help tumors grow, and it also stops the formation of new blood vessels that tumors need to grow. This makes it a potential new option for treating this type of cancer. ^{1 3 4 10 11}

How is the drug Tasquinimod unique in treating multiple myeloma?

Tasquinimod is unique because it targets the tumor microenvironment by inhibiting the S100A9 protein, which helps reduce the immunosuppressive activity of myeloid cells and suppresses tumor growth. It also has anti-angiogenic effects, meaning it can prevent the formation of new blood vessels that tumors need to grow, making it a novel approach compared to traditional treatments. ^{1 3 4 10 11}

Research Team

Dan Vogl, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

Adults diagnosed with relapsed or refractory multiple myeloma, who have measurable disease and are in relatively good health (ECOG ≤2), can join this trial. They must not be pregnant, agree to use contraception, and meet specific lab criteria. Exclusions include recent chemotherapy, certain medical conditions like active infections or severe cardiovascular issues, known allergies to study drugs, and prior treatment with tasquinimod.

Inclusion Criteria

For women of childbearing potential, a negative serum or urine pregnancy test prior to study treatment

I have been diagnosed with multiple myeloma.

I am not postmenopausal or surgically sterile and agree to use two forms of birth control.

Exclusion Criteria

I am currently undergoing treatment.

I do not have active tuberculosis, hepatitis A, B, C, or HIV.

I am currently on antibiotics or IV medication for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Tasquinimod single agent dose escalation to establish maximum tolerated dose (MTD) and optimal schedule

Variable, up to 3 years

Combination Therapy

Tasquinimod in combination with ixazomib, lenalidomide, and dexamethasone to establish combination MTD and optimal schedule

Variable, up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tasquinimod

Trial Overview The trial is testing a new drug called tasquinimod for multiple myeloma that has come back or didn't respond to treatment. It's being compared with IRd chemotherapy regimen. Tasquinimod inhibits S100A9 which could help control the progression of cancer.

Participant Groups

Group I: B2: Tasquinimod+IRd expansion Experimental Treatment 2 Interventions

Additional subjects will enroll in arm B2 at the MTD and optimal schedule, so that 12 subjects total who are both evaluable for response and previously refractory to their most recent Imid/PI combination will have received the MTD/optimal schedule of tasquinimod in combination with ixazomib, lenalidomide, and dexamethasone. To facilitate rapid enrollment and gain more experience with the combination therapy, up to 12 additional subjects with triple-class refractory myeloma (who are not previously refractory to their most recent Imid/PI combination) may be enrolled in cohort B2. Enrollment in arm B2 will not begin until enrollment in arm B1 has been completed and a combination MTD/optimal schedule has been established.

Group II: B1: Tasquinimod+IRd dose escalation Experimental Treatment 2 Interventions

Dose levels will be defined according to the same tasquinimod doses as in the single agent (Arm A1) dose escalation. Enrollment in arm B1 will not begin until enrollment in arm A1 has been completed and an MTD/optimal schedule has been established for single agent tasquinimod. Initial subjects in arm B1 will be enrolled at the lower of dose level 1 or one dose level below the single agent MTD . If this initial dose level is determined to exceed the combination MTD, further subjects will be enrolled at one dose level lower. Enrollment is not planned in arm B1 at doses higher than the single agent MTD. There are 9-12 planned subjects if all dose levels are explored.

Group III: A2: Tasquinimod single agent expansion Experimental Treatment 1 Intervention

Additional subjects will enroll in arm A2 at the MTD and optimal schedule, so that 12 subjects total who are evaluable for response will have received the MTD/optimal schedule of single agent tasquinimod. Enrollment in arm A2 will not begin until enrollment in arm A1 has been completed and a single agent MTD/optimal schedule has been established.

Group IV: A1: Tasquinimod single agent dose escalation Experimental Treatment 1 Intervention

There are up to 5 planned dose levels, with 3 de-escalation dose levels available in case dose level 1 is determined to exceed the MTD. This arm will enroll 15-30 subjects if all dose levels are explored.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Active Biotech AB

Industry Sponsor

Trials

12

Recruited

2,200+

Findings from Research

Tasquinimod has shown effectiveness in inhibiting the formation of metastases in castration-resistant prostate cancer, as demonstrated in both orthotopic and intratibial xenograft models.

The treatment appears to work by inducing molecular changes, such as upregulating thrombospondin 1 and downregulating hypoxia-driven genes, which contribute to its anti-angiogenic and anti-metastatic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). Jennbacken, K., Welén, K., Olsson, A., et al.[2017]

Novel agents like immunomodulatory drugs (IMiDs) and proteasome inhibitors (such as bortezomib) have significantly improved treatment outcomes for myeloma, showing better responses when used in combination with steroids and chemotherapy.

These therapies, initially used for relapsed or refractory myeloma, are now being tested in newly diagnosed patients, leading to higher response rates and longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for multiple myeloma. Dingli, D., Rajkumar, SV.[2009]

Tasquinimod significantly suppresses the establishment and growth of prostate cancer tumors in the bone of castrated mice, indicating its potential as a treatment for metastatic prostate cancer.

The drug appears to work by altering the bone microenvironment, reducing immunosuppression, and affecting bone remodeling processes, which may help prevent new metastatic lesions from forming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasquinimod inhibits prostate cancer growth in bone through alterations in the bone microenvironment. Magnusson, LU., Hagberg Thulin, M., Plas, P., et al.[2017]

Tasquinimod, currently in phase II trials for metastatic prostate cancer, shows anti-tumor activity by inhibiting tumor blood vessel formation (angiogenesis), primarily through the up-regulation of the protein thrombospondin-1 (TSP1).

In animal studies, tasquinimod treatment led to significant tumor growth inhibition, associated with decreased levels of HIF-1 alpha and VEGF proteins, indicating a mechanism that reduces angiogenesis and supports its potential as an effective cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors. Olsson, A., Björk, A., Vallon-Christersson, J., et al.[2021]

Immunomodulatory agents (IMiDs) like thalidomide and lenalidomide have significantly improved treatment options for multiple myeloma (MM), with pomalidomide showing promise in early clinical trials.

Pomalidomide may be effective in patients who have developed resistance to lenalidomide, suggesting that different IMiDs have unique mechanisms of action and that molecular biomarkers could help identify responsive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel immunomodulatory compounds in multiple myeloma. Saini, N., Mahindra, A.[2018]

In a study of 2587 elderly patients with advanced multiple myeloma, those treated with novel agents (proteasome inhibitors and immunomodulatory drugs) had a significantly increased risk of adverse events, including anemia, peripheral neuropathy, and thromboembolic events.

Combination therapies using both proteasome inhibitors and immunomodulatory drugs also showed a higher risk for anemia, neutropenia, and thromboembolic events compared to single-agent therapies, indicating that while these treatments are effective, they come with notable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma. Chen, Y., Lairson, DR., Chan, W., et al.[2018]

In a pooled analysis of 1088 heavily pretreated patients with relapsed and refractory multiple myeloma, pomalidomide combined with low-dose dexamethasone demonstrated an acceptable safety profile, with the most common severe adverse events being neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%).

Adverse events were effectively managed through dose modifications and supportive care, with 24.2% of patients requiring dose reductions and 66.0% experiencing treatment interruptions, indicating that while side effects were significant, they were manageable to allow continued therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Moreau, P., Dimopoulos, MA., Richardson, PG., et al.[2018]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

In a clinical trial involving 345 patients with refractory multiple myeloma, the combination of pomalidomide and dexamethasone (Pom/dex) showed a confirmed response rate of 35%, with better outcomes in patients who had undergone fewer prior treatments.

The study found that the 2 mg dose of pomalidomide resulted in longer treatment durations, higher response rates, and fewer adverse events, with median progression-free survival of 13.1 months and overall survival of 47.9 months, indicating its potential effectiveness in managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial. Ailawadhi, S., Mikhael, JR., LaPlant, BR., et al.[2019]

Tasquinimod significantly inhibits multiple myeloma (MM) cell proliferation and colony formation in vitro, while also enhancing T cell proliferation and functionality by targeting myeloid cells, suggesting a dual mechanism of action.

In vivo studies using 5TMM mouse models showed that tasquinimod reduced tumor load, increased trabecular bone volume, and improved overall survival, highlighting its potential as an effective immunomodulatory treatment for MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma. Fan, R., Satilmis, H., Vandewalle, N., et al.[2023]

Tasquinimod is a small molecule that inhibits tumor growth and metastasis by targeting the tumor microenvironment, enhancing the immune response, and reducing angiogenesis, making it a promising anti-cancer agent.

It specifically modulates myeloid cells in the tumor environment, shifting them towards a less immunosuppressive state, and works by blocking key protein interactions that promote tumor growth, indicating its potential for use in various solid tumors either alone or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of action of tasquinimod on the tumour microenvironment. Raymond, E., Dalgleish, A., Damber, JE., et al.[2022]

References

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

Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050). [2017]

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

Emerging therapies for multiple myeloma. [2009]

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

Tasquinimod inhibits prostate cancer growth in bone through alterations in the bone microenvironment. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Novel immunomodulatory compounds in multiple myeloma. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma. [2018]

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

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Mechanisms of action of tasquinimod on the tumour microenvironment. [2022]