OPN-6602 + Dexamethasone for Multiple Myeloma

Recruiting at 9 trial locations

Overseen By Kerry Inokuchi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Opna Bio LLC

Must not be taking: High-dose corticosteroids

Disqualifiers: Active plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1b, open-label study evaluating the safety, tolerability, pharmacokinetics, preliminary antitumor activity, and pharmacodynamics of OPN-6602 monotherapy and in combination with dexamethasone in subjects with relapsed and/or refractory MM.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take high-dose corticosteroids unless they are for conditions other than myeloma. Also, you must not have had chemotherapy, targeted anticancer, or radiation therapy within 2 weeks before starting the trial.

What data supports the effectiveness of the drug OPN-6602 + Dexamethasone for treating multiple myeloma?

Dexamethasone, a component of the treatment, has been a key part of multiple myeloma therapy for many years, often used in combination with other drugs to improve patient outcomes. Studies have shown that dexamethasone, when combined with other agents, can lead to good response rates in multiple myeloma patients. ^{1 2 3 4 5}

Is the combination of OPN-6602 and Dexamethasone safe for humans?

Dexamethasone, when used with other treatments like bortezomib for multiple myeloma, has shown some common side effects such as low blood cell counts, diarrhea, and nerve damage, but is generally considered safe in clinical settings. However, specific safety data for OPN-6602 is not provided in the available research. ^{3 5 6 7 8}

How is the drug OPN-6602 + Dexamethasone different from other treatments for multiple myeloma?

The combination of OPN-6602 with dexamethasone is unique because it potentially offers a novel mechanism of action or formulation that could enhance treatment adherence and reduce pill burden, unlike traditional regimens that often require complex administration methods like intravenous catheters. ^{1 2 3 5 9}

Eligibility Criteria

This trial is for people with Multiple Myeloma that has come back or didn't respond to treatment. Participants should have tried at least two prior therapies and be in good enough health for the study.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

My blood, kidney, liver, and heart are functioning well.

My multiple myeloma has not responded to 3 types of treatments including immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibody.

Exclusion Criteria

I have active plasma cell leukemia.

I haven't had cancer treatment or radiation in the last 2 weeks.

I am currently receiving treatment for an infection through injections or IV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive OPN-6602 monotherapy or in combination with dexamethasone to determine the maximum tolerated dose

8-12 weeks

Dose Expansion

Participants receive the determined dose of OPN-6602 to further assess safety and preliminary antitumor activity

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexamethasone
• OPN-6602

Trial Overview The trial is testing OPN-6602, alone and combined with Dexamethasone, to see how safe it is and if it works against Multiple Myeloma that's hard to treat.

Participant Groups

Group I: Dose expansion Experimental Treatment 1 Intervention

Group II: Dose escalation monotherapy Experimental Treatment 1 Intervention

Group III: Dose escalation in combo with dexamethasone Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Opna Bio LLC

Lead Sponsor

Trials

5

Recruited

260+

Findings from Research

Dexamethasone remains a crucial part of multiple myeloma treatment, enhancing the effectiveness of novel therapies and improving response rates across all treatment phases.

New formulations of dexamethasone aim to reduce the number of pills patients need to take, which could help improve adherence to treatment and minimize medication errors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From mechanism to resistance - changes in the use of dexamethasone in the treatment of multiple myeloma. Rosenberg, AS.[2023]

In a study of multiple myeloma patients treated between 1997 and 2005, the combination of thalidomide and dexamethasone (Thal/dex) resulted in a significantly higher response rate of 84.3% compared to 55% for the VAD chemotherapy regimen.

Thal/dex not only induced higher complete responses (CR) and very good partial responses (VGPR) but also avoided complications associated with intravenous catheters used in VAD, making it a safer and more effective treatment option for newly diagnosed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vincristine, doxorubicin, and dexamethasone or thalidomide plus dexamethasone for newly diagnosed patients with multiple myeloma? Jimenez-Zepeda, VH., Domínguez-Martínez, VJ.[2015]

In a study of three human myeloma cell lines, dexamethasone effectively caused growth arrest, but this effect was completely reversed by low levels of IL-6, indicating that IL-6 plays a significant role in steroid escape in multiple myeloma.

Other cytokines like LIF and OSM also counteracted the growth inhibition caused by dexamethasone, suggesting that the presence of these cytokines in the tumor environment can diminish the effectiveness of steroid treatments in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells. Juge-Morineau, N., François, S., Puthier, D., et al.[2019]

Pomalidomide combined with low-dose dexamethasone (POM + LoDEX) significantly improves overall survival in patients with relapsed/refractory multiple myeloma compared to high-dose dexamethasone, with a median overall survival of 22.4 months for those achieving at least a partial response.

Patients with stable disease (SD) at cycle 3 showed improved responses by cycle 7, indicating that even those not showing immediate improvement can benefit from POM + LoDEX treatment, suggesting it should be a standard option after other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). Moreau, P., Weisel, KC., Song, KW., et al.[2019]

In a phase II study involving 49 previously untreated multiple myeloma patients, the combination of bortezomib and dexamethasone resulted in a high overall response rate of 90%, with 42% achieving at least a very good partial response and 19% reaching complete or near-complete response.

After a median follow-up of 49 months, the treatment showed promising long-term outcomes, with an estimated 4-year survival rate of 67%, indicating that bortezomib with or without dexamethasone is an effective and well-tolerated option for frontline therapy in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma. Jagannath, S., Durie, BG., Wolf, JL., et al.[2015]

In a phase 3b trial involving 638 patients with relapsed or refractory multiple myeloma, bortezomib demonstrated a 67% overall response rate, indicating it is an effective treatment option for heavily pretreated patients.

The combination of bortezomib with dexamethasone improved responses in 34% of patients who received it, although common side effects included thrombocytopenia and neuropathy, with 25% of patients experiencing some level of neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Mikhael, JR., Belch, AR., Prince, HM., et al.[2022]

Oxaliplatin (L-OHP) effectively inhibits the growth of multiple myeloma (MM) cells at concentrations achievable in therapy, showing greater activity than Cisplatin and Carboplatin, with an IC(50) of 5-10 microM after 24 hours.

The combination of L-OHP with Dexamethasone enhances anti-myeloma effects and induces apoptotic cell death, suggesting a promising therapeutic strategy for treating MM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin (L-OHP) treatment of human myeloma cells induces in vitro growth inhibition and apoptotic cell death. Tassone, P., Tagliaferri, P., Galea, E., et al.[2019]

Dexamethasone effectively inhibits the growth of multiple myeloma cells by reducing the expression of interleukin-6 (IL-6) and its receptor, particularly at concentrations of 10(-7) to 10(-6) mol/L, in three out of four tested cell lines.

The study suggests that blocking the IL-6 signaling pathway is crucial for the effectiveness of dexamethasone in killing myeloma cells, as the presence of IL-6 can reverse the cell-killing effects of dexamethasone without affecting the glucocorticoid receptor's function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-6 prevents dexamethasone-induced myeloma cell death. Hardin, J., MacLeod, S., Grigorieva, I., et al.[2021]

Inhibition of the IL-6 signaling pathway using the superantagonist Sant7 significantly enhances the effectiveness of dexamethasone in reducing tumor growth in a murine model of multiple myeloma, as indicated by a synergistic reduction in serum levels of the soluble IL-6 receptor.

The combination treatment of Sant7 and dexamethasone led to changes in gene expression that promote apoptosis and inhibit cell proliferation in multiple myeloma cells, suggesting a promising therapeutic strategy for improving patient outcomes in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu In vivo model of human multiple myeloma. Tassone, P., Neri, P., Burger, R., et al.[2013]

References

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

From mechanism to resistance - changes in the use of dexamethasone in the treatment of multiple myeloma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Vincristine, doxorubicin, and dexamethasone or thalidomide plus dexamethasone for newly diagnosed patients with multiple myeloma? [2015]

3. England pubmed.ncbi.nlm.nih.gov

The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells. [2019]

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

Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). [2019]

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

Extended follow-up of a phase 2 trial of bortezomib alone and in combination with dexamethasone for the frontline treatment of multiple myeloma. [2015]

6. England pubmed.ncbi.nlm.nih.gov

High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. [2022]

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

Oxaliplatin (L-OHP) treatment of human myeloma cells induces in vitro growth inhibition and apoptotic cell death. [2019]

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

Interleukin-6 prevents dexamethasone-induced myeloma cell death. [2021]

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

Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu In vivo model of human multiple myeloma. [2013]