Eftozanermin Alfa + Bortezomib + Dexamethasone for Multiple Myeloma

Recruiting at 27 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: Bortezomib, Dexamethasone

Must not be taking: Monoclonal antibodies

Disqualifiers: Liver disease, Eye conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 44 weeks

4 Participants Needed

Trial Summary

What is the purpose of this trial?

Multiple myeloma (MM) is a rare cancer caused by abnormal survival of plasma cells (blood cells). Most trial participants with MM relapse (cancer has come back) or become non- responsive to treatment and remission gets shorter after each line of treatment. This is a study to determine recommended Phase 2 dose and change in disease symptoms of eftozanermin alfa in combination with bortezomib and dexamethasone to assess how efficient the treatment is in adult participants with relapsed/refractory (R/R) MM. Eftozanermin alfa (ABBV-621) is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. Participants in one arm will receive different doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine phase 2 dose (RP2D). Participants in the other arm will receive eftozanermin alfa at RP2D in combination with bortezomib and dexamethasone. Around 40 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 20 sites across the world. Participants will receive eftozanermin alfa as an infusion into the vein in combination with bortezomib as an infusion into the vein or an injection under the skin and oral dexamethasone tablets for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot have received certain treatments like bortezomib recently or other specific therapies within a certain time frame before starting the trial. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug combination Eftozanermin Alfa, Bortezomib, and Dexamethasone for treating multiple myeloma?

Research shows that combining bortezomib and dexamethasone is effective for treating relapsed multiple myeloma, and adding other drugs like selinexor can improve response rates. This suggests that combining these drugs with Eftozanermin Alfa might also be effective. ^{1 2 3 4 5}

Is the combination of Eftozanermin Alfa, Bortezomib, and Dexamethasone safe for humans?

Bortezomib and dexamethasone, used together, have been studied for multiple myeloma and are generally considered safe, though they can cause side effects like low blood cell counts, diarrhea, and nerve damage. Eftozanermin Alfa's safety in combination with these drugs isn't detailed here, but the existing data on bortezomib and dexamethasone suggests they are manageable with medical supervision. ^{3 4 6 7 8}

What makes the drug combination of Eftozanermin Alfa, Bortezomib, and Dexamethasone unique for treating multiple myeloma?

The combination of Eftozanermin Alfa with Bortezomib and Dexamethasone is unique because it includes Eftozanermin Alfa, which is not commonly used in standard treatments for multiple myeloma. This combination may offer a novel approach by potentially enhancing the effectiveness of Bortezomib and Dexamethasone, which are already established treatments for this condition. ^{2 4 9 10 11}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with Multiple Myeloma who've had 3-6 prior treatments including specific agents, but whose cancer has returned or stopped responding to treatment. They must have measurable disease, a life expectancy of at least 12 weeks, and good heart, liver, and kidney function. Not eligible if they've had recent bortezomib therapy or certain eye surgeries, uncontrolled liver issues, high-dose steroids recently, other MM therapies too close to the trial start date or severe neuropathy.

Inclusion Criteria

I have been diagnosed with multiple myeloma according to IMWG standards.

My cancer can be measured by specific blood or urine tests.

My multiple myeloma has returned or didn't respond after 3-6 treatments including IMiD, PI, and anti-CD38.

Exclusion Criteria

I stopped taking bortezomib because of side effects.

I haven't taken high doses of steroids recently.

I haven't received monoclonal antibodies for myeloma in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eftozanermin alfa in combination with bortezomib and dexamethasone for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12.

44 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bortezomib
• Dexamethasone
• Eftozanermin alfa

Trial Overview The study is testing Eftozanermin alfa (ABBV-621) combined with Bortezomib and Dexamethasone in adults with relapsed/refractory Multiple Myeloma. Participants are divided into two groups: one receives varying doses to find the optimal Phase 2 dose; the other gets this determined dose for comparison. The drugs are given over several cycles involving IV infusions and oral tablets.

Participant Groups

Group I: Safety Lead-in Experimental Treatment 3 Interventions

Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).

Group II: Dose Expansion Experimental Treatment 3 Interventions

Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

The MUK Five trial is a phase II study comparing the effectiveness of a new combination treatment (carfilzomib, cyclophosphamide, and dexamethasone) against the standard treatment (cyclophosphamide, bortezomib, and dexamethasone) in patients with multiple myeloma at first relapse, involving participants who have received no more than one prior treatment.

The trial aims to determine if the new combination (CCD) is at least as effective as the standard treatment (CVD) in achieving significant response rates, while also assessing the potential benefits of maintenance therapy with carfilzomib for improving progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. Brown, S., Hinsley, S., Ballesteros, M., et al.[2022]

In a study of 669 patients with relapsed multiple myeloma, bortezomib demonstrated significantly higher response rates and longer survival compared to high-dose dexamethasone, with complete response rates of 6% versus less than 1%.

Patients treated with bortezomib had a median time to progression of 6.22 months compared to 3.49 months for those on dexamethasone, indicating bortezomib's greater efficacy in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. Richardson, PG., Sonneveld, P., Schuster, MW., et al.[2022]

In two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

In a phase 3 trial involving 402 patients with previously treated multiple myeloma, the combination of selinexor, bortezomib, and dexamethasone resulted in a median progression-free survival of 13.93 months, significantly longer than the 9.46 months observed with standard bortezomib and dexamethasone (p=0.0075).

The selinexor combination therapy was associated with lower rates of peripheral neuropathy (21%) compared to the standard treatment (34%), suggesting a safer profile regarding this common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Grosicki, S., Simonova, M., Spicka, I., et al.[2022]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

In a study of 24 multiple myeloma patients treated with bortezomib and dexamethasone, 79.2% showed a positive response, with a notably higher complete remission rate in light-chain type patients (57.1%) compared to non-light-chain type patients (5.9%).

The treatment was found to be safe for patients with renal impairment, as their renal function improved during chemotherapy, and the adverse events were manageable, with most patients tolerating the side effects well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. Li, J., Zhao, Y., Luo, SK., 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]

In a phase 1/2 trial involving 65 patients with newly diagnosed multiple myeloma, the combination of oral ixazomib, lenalidomide, and dexamethasone was found to be generally well tolerated, with a maximum tolerated dose of ixazomib established at 2.97 mg/m².

The treatment resulted in a very good partial response or better in 58% of patients, indicating significant efficacy and supporting further phase 3 trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Kumar, SK., Berdeja, JG., Niesvizky, R., et al.[2019]

In a study involving 929 patients with relapsed or refractory multiple myeloma, carfilzomib combined with dexamethasone significantly improved median progression-free survival (18.7 months) compared to bortezomib with dexamethasone (9.4 months), indicating greater efficacy of carfilzomib.

While both treatments had serious adverse events, carfilzomib was associated with a higher rate of serious adverse events (48%) compared to bortezomib (36%), suggesting that while carfilzomib may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Dimopoulos, MA., Moreau, P., Palumbo, A., et al.[2022]

References

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

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. [2022]

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

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. [2022]

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

Effective treatment of advanced multiple myeloma refractory to alkylating agents. [2015]

6. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. [2015]

7. China pubmed.ncbi.nlm.nih.gov

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. [2015]

8. 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]

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

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. [2019]

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

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Bortezomib and dexamethasone in previously untreated multiple myeloma associated with renal failure and reversal of renal failure. [2015]