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

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety and side effects of SX-682 in combination with standard of care treatment carfilzomib, daratumumab-hyaluronidase, and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). SX-682 works by blocking certain sites on cells that suppress the ability of the immune system to destroy tumor cells. Blocking those specific sites allows other cells of the immune system to become "free" to kill tumor cells. Carfilzomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and tumor cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill tumor cells, while hyaluronidase helps to deliver daratumumab to CD38-expressing tumor cells through a subcutaneous injection. Dexamethasone is in a class of medications called corticosteroids. It is known to kill myeloma cells and is also used to reduce inflammation and lower the body's immune response to monoclonal antibodies like dratumumab and help lessen its side effects. Giving SX-682 in combination with carfilzomib, daratumumab-hyaluronidase and dexamethasone may be safe and tolerable in treating patients with relapsed or refractory multiple myeloma

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.

What data supports the effectiveness of the drug combination SX-682, Carfilzomib, Daratumumab, Recombinant Human Hyaluronidase, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Carfilzomib, Daratumumab, and Dexamethasone is effective for patients with relapsed multiple myeloma, especially those who are resistant to other treatments. This combination has been approved by the US FDA for relapsed multiple myeloma patients, demonstrating strong clinical efficacy. ^{1 2 3 4 5}

Is the combination of SX-682, Carfilzomib, Daratumumab, and Dexamethasone safe for humans?

Daratumumab, when used with other drugs like Carfilzomib and Dexamethasone, has shown tolerable safety in treating multiple myeloma. Common side effects include infusion reactions, diarrhea, and upper respiratory infections, but these are generally manageable. The combination has been approved by the FDA for use in certain patients with multiple myeloma. ^{1 6 7 8 9}

What makes the SX-682 combination treatment for multiple myeloma unique?

The SX-682 combination treatment for multiple myeloma is unique because it includes a novel component, SX-682, alongside standard drugs like carfilzomib and daratumumab. This combination aims to enhance treatment efficacy, especially in patients who are resistant to other therapies, and the use of subcutaneous daratumumab reduces administration time and infusion-related reactions compared to the traditional intravenous method. ^{1 7 10 11 12}

Research Team

Jens Hillengass, MD

Principal Investigator

Roswell Park

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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, 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]

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]

References

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

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related quality of life of carfilzomib- and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma, based on German benefit assessment data. [2023]

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

Carfilzomib 56 mg/m2 twice-weekly in combination with dexamethasone and daratumumab (KdD) versus daratumumab in combination with bortezomib and dexamethasone (DVd): a matching-adjusted indirect treatment comparison. [2022]

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

Practical Considerations for Antibodies in Myeloma. [2019]

5. United States 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. [2021]

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

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]

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

Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. [2021]

8. England 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. [2020]

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

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. [2022]

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

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. [2021]