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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, tasquinimod, for people with multiple myeloma, a type of blood cancer. Researchers aim to assess the safety and effectiveness of tasquinimod, both alone and in combination with other medications. The trial includes different groups to explore various doses and combinations to identify the best treatment plan. Individuals whose multiple myeloma has returned or who haven't responded to past treatments might be suitable for this trial.

As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Research has shown that tasquinimod is generally well tolerated by people with relapsed or refractory multiple myeloma, a type of blood cancer. Previous studies found that it works effectively both on its own and when combined with other treatments like ixazomib, lenalidomide, and dexamethasone (known together as IRd). For those taking tasquinimod alone, the optimal dose was 1 mg daily.

Evidence indicates that tasquinimod helps fight cancer cells. When used with IRd, tasquinimod also produced positive results in several patients. No major safety issues emerged in these studies, suggesting that tasquinimod is a promising treatment option with a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about tasquinimod for multiple myeloma because it offers a novel approach compared to standard treatments, which typically include proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Tasquinimod works uniquely by targeting the tumor microenvironment, potentially limiting cancer growth by disrupting the blood supply to the tumor. This mechanism of action differs from the direct targeting of multiple myeloma cells seen in existing therapies. Additionally, tasquinimod is being explored both as a single agent and in combination with other treatments, which could enhance its effectiveness and provide new options for patients, particularly those who are refractory to current therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that tasquinimod may help treat multiple myeloma, a type of blood cancer. In early studies, tasquinimod slowed the growth of myeloma cells and prevented them from forming clusters. It has shown potential as a treatment, particularly for patients whose cancer has returned or is difficult to treat. Tasquinimod works by blocking a protein called S100A9, which aids myeloma cell growth. In this trial, some participants will receive tasquinimod alone, while others will receive it with drugs like ixazomib, lenalidomide, and dexamethasone (IRd). When combined with these drugs, tasquinimod has demonstrated activity against myeloma and is generally well tolerated, leading to positive patient outcomes. These findings suggest that tasquinimod could be an effective treatment option for multiple myeloma. ^{1 2 6 7 8}

Who Is on the Research Team?

Dan Vogl, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. activebiotech.com activebiotech.com/en/mfn_news/results-from-tasquinimod-study-in-heavily-pretreated-patients-with-relapsed-refractory-multiple-myeloma-presented-at-asco-2025-available-on-active-biotechs-website/

Results from tasquinimod study in heavily pretreated ... Tasquinimod has demonstrated a clear therapeutic potential in preclinical models of multiple myeloma, when used as a single agent and in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7555

Clinical activity of novel targeting of S100A9 with ... Conclusions: Tasquinimod, an S100A9 inhibitor, is well tolerated in combination with IRd and has anti-myeloma activity, as evidenced by ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124098859

Tasquinimod, an S100A9 Inhibitor, in Combination with ... Tasquinimod, an S100A9 inhibitor, is well tolerated in combination with IRd and has anti-myeloma activity, as evidenced by three clinical responses.

4. activebiotech.com activebiotech.com/en/mfn_news/active-biotech-reports-study-results-with-tasquinimod-in-heavily-pre-treated-patients-with-relapsed-refractory-multiple-myeloma/

Active Biotech reports study results with tasquinimod in ... The results confirm that tasquinimod has anti-myeloma activity and is well tolerated in patients previously refractory to Imid/PI combination therapy.

5. researchgate.net researchgate.net/publication/386484518_Tasquinimod_an_S100A9_Inhibitor_in_Combination_with_Ixazomib_Lenalidomide_and_Dexamethasone_for_Relapsed_and_Refractory_Multiple_Myeloma

Tasquinimod, an S100A9 Inhibitor, in Combination with ... We previously reported preliminary results of a phase 1 trial of tasq alone and in combination with ixazomib (ixa), lenalidomide (len), and ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8042

Phase 1 study of tasquinimod, an S100A9 inhibitor, alone ... Tasquinimod, an S100A9 inhibitor, is well tolerated in pts with RRMM as a single-agent and in combination with IRd, with a single-agent MTD of 1 mg daily after ...

7. inderes.dk inderes.dk/en/releases/active-biotech-announces-first-patient-dosed-in-the-combination-part-of-the-phase-ibiia-study-of-tasquinimod-in-multiple-myeloma

Active Biotech announces first patient dosed in ... - Inderes.dk Tasquinimod has demonstrated a clear therapeutic potential in preclinical models of multiple myeloma, when used as a single agent and in combination with ...

8. healthtree.org healthtree.org/myeloma/community/podcasts/tasquinimod-as-a-new-myeloma-therapy

Tasquinimod As a New Myeloma Therapy with Dan Vogl Learn more about this clinical trial using tasquinimod with ixazomib, lenalidomide and dex in combination to improve myeloma outcomes and slow myeloma growth.