Tasquinimod for the Treatment of Relapsed or Refractory Myeloma

NCT04405167 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 842603, UPCC 45419UPCC 45419
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Optimal Dose

  Maximum tolerated dose of single agent tasquinimod (mg).

  approximately 3 years

Secondary Outcomes (4)

• Preliminary Single-Agent Toxicity Profile

  approximately 3 years

• Preliminary Combination Therapy Toxicity Profile

  approximately 3 years

• Preliminary Single-Agent Response

  approximately 3 years

• Preliminary Assessment of Clinical Response Combination Therapy

  approximately 3 years

Study Arms (4)

A1: Tasquinimod single agent dose escalation

EXPERIMENTAL

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.

Drug: Tasquinimod

A2: Tasquinimod single agent expansion

EXPERIMENTAL

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.

Drug: Tasquinimod

B1: Tasquinimod+IRd dose escalation

EXPERIMENTAL

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.

Drug: Tasquinimod; Drug: IRd chemotherapy

B2: Tasquinimod+IRd expansion

EXPERIMENTAL

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.

Drug: Tasquinimod; Drug: IRd chemotherapy

Interventions

Tasquinimod DRUG

Tasquinimod will be supplied as oral capsules.

A1: Tasquinimod single agent dose escalation; A2: Tasquinimod single agent expansion; B1: Tasquinimod+IRd dose escalation; B2: Tasquinimod+IRd expansion

IRd chemotherapy DRUG

IRd chemotherapy with ixazomib, lenalidomide, and dexamethasone

Also known as: Ixazomib, Lenalidomide, Dexamethasone

B1: Tasquinimod+IRd dose escalation; B2: Tasquinimod+IRd expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• years of age or older
• Multiple myeloma (MM) diagnosed according to IMWG criteria
• Measurable disease (this is defined differently in different arms)
• Multiple myeloma relapsed or refractory to treatment (this is defined differently in different arms)
• Meet certain clinical laboratory criteria
• ECOG performance status ≤2
• Life expectancy of at least 3 months
• For women of childbearing potential, a negative serum or urine pregnancy test prior to study treatment.
• For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two methods of contraception one of which must be highly effective
• For men: agreement to use a barrier method of contraception for 1 month before start of study treatment, during the treatment period and for 6 months after the last dose of study treatment.

You may not qualify if:

• Failure to have fully recovered (i.e. ≤ Grade 1 toxicity) from the effects of prior chemotherapy (except for alopecia)
• Active graft versus host disease
• Treatment with any of the following:
• Cytotoxic chemotherapy within 3 weeks prior to the initiation of study treatment
• Proteasome inhibitors, Imids, or monoclonal antibodies within 2 weeks prior to the initiation of study treatment
• Experimental therapy within 4 weeks or 5 half-lives, whichever is shorter
• Systemic corticosteroids \>=10 mg prednisone or equivalent within 7 days prior to the initiation of study treatment
• Radiotherapy within 7 days prior to initiating study treatment
• Plasmapheresis within 4 weeks prior to the initiation of study treatment
• Tasquinimod at any time
• Known central nervous system involvement by myeloma
• Diagnosis of smoldering multiple myeloma
• Diagnosis of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Active plasma cell leukemia
• Symptomatic primary (AL) amyloidosis

Sponsors & Collaborators

• University of Pennsylvania: lead
• Active Biotech AB: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Fan R, Satilmis H, Vandewalle N, Verheye E, Vlummens P, Maes A, Muylaert C, De Bruyne E, Menu E, Evans H, Chantry A, De Beule N, Hose D, Torngren M, Eriksson H, Vanderkerken K, Maes K, Breckpot K, De Veirman K. Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma. J Immunother Cancer. 2023 Jan;11(1):e005319. doi: 10.1136/jitc-2022-005319.

  PMID: 36650020 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

tasquinimod; ixazomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Dan Vogl, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label phase 1 study with pilot expansion cohorts at the maximum tolerated dose

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: May 28, 2020
• Study Start: July 10, 2020
• Primary Completion: May 19, 2025
• Study Completion: July 1, 2025
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)