SX-682 + Standard Treatments for Multiple Myeloma

Overseen By ASK RPCI

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Carfilzomib, Daratumumab, Dexamethasone

Must not be taking: CYP3A4 inhibitors, QT prolonging

Disqualifiers: Non-secretory myeloma, Heart failure, Hepatitis, others

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, SX-682, combined with standard treatments to determine its safety and effectiveness for people with multiple myeloma, a type of blood cancer that has returned or resisted other treatments. SX-682 is designed to enhance the immune system's ability to fight cancer cells. Participants will receive SX-682 along with carfilzomib, daratumumab-hyaluronidase, and dexamethasone, existing treatments that help stop cancer cell growth and boost the immune response. Those with multiple myeloma that hasn't improved or has returned after treatment might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how SX-682 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot take medications that strongly affect certain liver enzymes (CYP3A4) or those that affect heart rhythm (QT prolonging), unless they are essential for your care and no alternatives exist.

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

Previous studies have shown that SX-682 is well-tolerated, meaning patients handled the treatment without severe side effects. No patients stopped treatment due to negative reactions, suggesting SX-682 is safe.

Carfilzomib, daratumumab-hyaluronidase, and dexamethasone are standard treatments for multiple myeloma and have been approved for use, indicating they have undergone safety testing. These drugs are generally well-tolerated, though they can have side effects, as with all medications. They are widely used in treating multiple myeloma.

Overall, combining SX-682 with these standard treatments appears safe, based on data from previous studies and the established use of the other medications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for multiple myeloma?

SX-682 is unique because it targets the CXCR1/2 pathway, which plays a role in cancer cell growth and survival. Unlike standard treatments like carfilzomib and daratumumab, which focus on disrupting cancer cell proteins or using immune cells to attack cancer, SX-682 works by interfering with signals that help myeloma cells thrive. Researchers are excited about this treatment because it offers a new mechanism of action that could enhance the effectiveness of existing therapies and potentially improve patient outcomes.

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

Research has shown that SX-682, which participants in this trial will receive, might help the immune system find and destroy cancer cells by blocking areas that usually weaken immune responses. Early results suggest that SX-682 is generally safe and could benefit patients who haven't improved with other treatments. In this trial, participants will also receive Carfilzomib, which stops enzymes that cancer cells need to grow, helping to slow the disease. Daratumumab targets a protein called CD38 on myeloma cells, assisting the immune system in attacking these cells. Dexamethasone, a type of steroid, reduces swelling and can enhance the effects of other treatments. Together, these treatments aim to improve outcomes for people with relapsed or hard-to-treat multiple myeloma. ^{1 4 6 7 8}

Who Is on the Research Team?

Jens Hillengass, MD

Principal Investigator

Roswell Park

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has relapsed or is refractory. Participants must have certain levels of specific proteins and cells in their blood and bone marrow, at least one prior therapy, and be planning to receive a treatment regimen including carfilzomib/daratumumab/dexamethasone. They should also be physically able to perform daily activities (ECOG 0-2).

Inclusion Criteria

Understanding of the investigational nature of the study and signing of informed consent form

Agreement to use adequate contraceptive methods for women of child-bearing potential

My blood counts and organ functions are within normal ranges.

Exclusion Criteria

Abnormal ECG findings or history of certain cardiac conditions

Pregnancy or nursing

Inability or unwillingness to follow protocol requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SX-682, daratumumab-hyaluronidase, carfilzomib, and dexamethasone in cycles of 28 days for up to 6 cycles

24 weeks

Weekly visits for the first 2 cycles, then bi-weekly visits for cycles 3-6

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Extension

Participants with sustained response may continue treatment cycles every 28 days

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab and Recombinant Human Hyaluronidase
• Dexamethasone
• SX-682

Trial Overview

The trial tests the safety of SX-682 combined with standard treatments: carfilzomib, daratumumab-hyaluronidase, and dexamethasone. SX-682 may help the immune system kill tumor cells by blocking suppressive cell sites. The combination aims to improve outcomes for those with relapsed/refractory multiple myeloma.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 10 Interventions

Patients receive SX-682 PO BID on days 1-21 of each cycle. Patients also receive daratumumab-hyaluronidase SC once weekly on cycles 1 and 2 and once every 2 weeks on cycles 3-6 and carfilzomib IV on days 1, 8 and 15 and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with sustained response after 6 cycles may continue to receive SX-682 PO BID on days 1-21, daratumumab-hyaluronidase SC on day 1, carfilzomib IV on days 1, 8, and 15 and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, BM aspiration, ECHO and PET/CT or MRI on study.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

Daratumumab, when combined with lenalidomide and dexamethasone or bortezomib and dexamethasone, significantly improves progression-free survival in patients with multiple myeloma who have received prior therapy, with reductions in the risk of disease progression or death by 63% and 61%, respectively.

The most common side effects reported were infusion reactions, diarrhea, and upper respiratory infections, with neutropenia and thrombocytopenia noted as important warnings, indicating that while daratumumab is effective, monitoring for these adverse reactions is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. Bhatnagar, V., Gormley, NJ., Luo, L., et al.[2022]

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

Daratumumab, now available in a subcutaneous form, significantly reduces administration time from 7 hours to just 3-5 minutes compared to the intravenous version, making it more convenient for patients.

The subcutaneous formulation also has lower rates of infusion-related reactions (less than 10% compared to 50% for intravenous), while maintaining similar efficacy and safety profiles, which enhances its overall usability in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. Sanchez, L., Richter, J., Cho, HJ., et al.[2021]

The combination of daratumumab, carfilzomib, and dexamethasone has shown strong clinical efficacy in treating relapsed multiple myeloma, particularly in patients whose disease is refractory to lenalidomide.

This triplet therapy has been approved by the US FDA for use in relapsed multiple myeloma, highlighting its significance as a treatment option in a setting with limited effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. Touzeau, C., Antier, C., Moreau, P.[2021]

Daratumumab, a monoclonal antibody targeting CD38, shows significantly improved overall survival in patients with multiple myeloma who have undergone extensive prior treatments, with an adjusted overall survival-hazard ratio of 0.33 based on a study of 148 patients compared to historical controls.

The study highlights that daratumumab is particularly effective in heavily pretreated patients, including those who are triple or quadruple refractory to other therapies, indicating its potential as a critical treatment option in advanced multiple myeloma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. Usmani, SZ., Diels, J., Ito, T., et al.[2021]

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