Belantamab Mafodotin + Pd vs Bortezomib + Pd for Multiple Myeloma
(DREAMM 8 Trial)
Recruiting in Palo Alto (17 mi)
+134 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: GlaxoSmithKline
Must not be taking: Monoclonal antibodies
Disqualifiers: Active infection, Cardiovascular risk, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).
Will I have to stop taking my current medications?
The trial requires that you stop taking any systemic anti-myeloma therapy, including chemotherapy and systemic steroids, within 14 days before starting the study drug. If you have been treated with a monoclonal antibody drug, you must wait 30 days before starting the study drugs.
What data supports the effectiveness of the drug combination Belantamab Mafodotin + Pd for treating multiple myeloma?
Pomalidomide combined with low-dose dexamethasone has shown effectiveness in patients with relapsed and refractory multiple myeloma, improving progression-free survival and overall response rates. Additionally, bortezomib-based regimens have been effective in improving overall survival in multiple myeloma patients.
12345What safety data exists for the combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone in treating multiple myeloma?
Bortezomib and dexamethasone have been studied for safety in multiple myeloma, with findings suggesting that adjusting the dose of bortezomib can reduce side effects like gastrointestinal issues. Additionally, a combination of pomalidomide, bortezomib, and dexamethasone has been used safely in patients with relapsed or refractory multiple myeloma, even with dose adjustments for older patients or those with other health conditions.
26789What makes the drug Belantamab Mafodotin unique for treating multiple myeloma?
Belantamab Mafodotin is unique because it is a first-in-class antibody-drug conjugate (a targeted therapy that combines an antibody with a drug) that specifically targets BCMA on myeloma cells, delivering a toxic substance directly to the cancer cells. This approach allows for a more targeted attack on the cancer, potentially leading to deep and durable responses in patients who have already tried multiple other treatments.
1011121314Eligibility Criteria
Adults with relapsed/refractory multiple myeloma who've had at least one prior therapy including lenalidomide, and have measurable disease. They must be in relatively good health (ECOG 0-2), possibly post-autologous stem cell transplant, and not have severe ongoing side effects from previous treatments. Excluded are those with certain infections, unstable liver or kidney conditions, recent heart issues or thromboembolism, active bleeding disorders, other cancers unless stable for 2 years, hypersensitivity to trial drugs or their components.Inclusion Criteria
I have had at least one treatment for my multiple myeloma, including a regimen with lenalidomide, and my disease has progressed after the most recent treatment.
All my side effects from previous cancer treatments are mild, except for hair loss.
I can take care of myself and am up and about more than half of my waking hours.
I have been diagnosed with multiple myeloma according to IMWG criteria.
I can take care of myself and am up and about more than half of my waking hours.
All my side effects from previous cancer treatments are mild, except for hair loss.
I had a stem cell transplant over 100 days ago or can't have one, and I don't have any active infections.
Exclusion Criteria
I have an ongoing kidney condition.
I have received treatment targeting BCMA before.
I have not undergone plasmapheresis within the last week.
I do not have cirrhosis or current liver problems.
I have ongoing nerve pain in my hands or feet, or severe nerve damage.
I am not allergic to belantamab mafodotin or similar drugs.
I haven't taken any myeloma treatment or monoclonal antibody drugs recently.
I have had blood clots in my veins or arteries in the last 3 months.
I cannot or do not want to take blood clot prevention medication as required by the study.
I have taken pomalidomide before or cannot tolerate it.
I have a mild eye condition but no serious corneal disease.
I am currently experiencing bleeding from an internal organ or mucosa.
I do not have active HIV, hepatitis B, or hepatitis C, or I meet specific criteria if I do.
I do not have active plasma cell leukemia, amyloidosis, POEMS syndrome, or related conditions.
I have had a stem cell transplant from a donor.
I am currently being treated for an infection.
Participant Groups
The trial is testing the effectiveness of belantamab mafodotin combined with pomalidomide and dexamethasone against a combination of pomalidomide, bortezomib and dexamethasone in treating multiple myeloma that has come back or didn't respond to treatment.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: Belantamab mafodotin plus Pomalidomide and DexamethasoneExperimental Treatment3 Interventions
Group II: Arm B: Bortezomib plus Pomalidomide and DexamethasoneActive Control3 Interventions
Belantamab mafodotin is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Blenrep for:
- Relapsed or refractory multiple myeloma (approval withdrawn)
🇪🇺 Approved in European Union as Blenrep for:
- Relapsed or refractory multiple myeloma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
GSK Investigational SitePembroke Pines, FL
GSK Investigational SiteSeattle, WA
GSK Investigational SitePittsburgh, PA
GSK Investigational SiteNashville, TN
More Trial Locations
Loading ...
Who is running the clinical trial?
GlaxoSmithKlineLead Sponsor
References
Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. [2020]Herein, we summarize the novel clinical data for multiple myeloma (MM) that were presented in the 2019 Annual Meeting of the American Society of Hematology. Triplet regimens including lenalidomide-dexamethasone for high-risk smoldering MM are effective but longer follow-up data are needed. Among transplant-eligible, newly diagnosed MM (NDMM) patients, carfilzomib- and daratumumab-based combinations are promising as effective and safe induction regimens and do not impair stem cell collection. Maintenance with ixazomib results in prolonged progression-free survival (PFS) compared with placebo. Regarding transplant-ineligible NDMM patients, large phase III studies showed that the additional use of daratumumab in backbone first-line regimens provides deep responses and PFS prolongation, whereas dose-/schedule-adjusted lenalidomide-dexamethasone has similar efficacy and is more tolerable than continuous lenalidomide-dexamethasone. In the relapsed/refractory setting carfilzomib- and daratumumab-based regimens remain highly effective and safe treatments, whereas the introduction of venetoclax, isatuximab, atezolizumab, and oprozomib broadens the therapeutic options. Among heavily pretreated MM patients, selinexor and melflufen showed particularly encouraging results. Novel immunotherapeutic approaches including chimeric antigen receptor T cells against B-cell maturation antigen and bispecific antibodies constitute a promising alternative that remains to be evaluated in later-phase studies.
Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. [2023]Traditional bortezomib, thalidomide, and dexamethasone (VTd) regimens for patients with newly diagnosed multiple myeloma (NDMM) include doses of thalidomide up to 200 mg/day (VTd-label). Clinical practice has evolved to use a lower dose (100 mg/day) to reduce toxicity (VTd-mod), which was evaluated in the phase III CASSIOPEIA study, without or with daratumumab (D-VTd; an anti-CD38 monoclonal antibody). We used propensity score matching to compare efficacy and safety for VTd-mod and D-VTd with VTd-label.
Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. [2021]Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone (Pom/dex) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly. Thirty-five patients were enrolled in each cohort. Confirmed responses in the 2-mg cohort consisted of very good partial response (VGPR) in 5 (14%), partial response (PR) in 4 (11%), minor response (MR) in 8 (23%) for an overall response rate of 49%. In the 4-mg cohort, confirmed responses consisted of complete response (CR) in 1 (3%), VGPR in 3 (9%), PR in 6 (17%), MR in 5 (14%) for an overall response rate of 43%. Overall survival at 6 months is 78% and 67% in the 2- and 4-mg cohort, respectively. Myelosuppression was the most common toxicity. This nonrandomized data suggests no advantage for 4 mg over the 2 mg daily. Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib. This trial is registered at http://ClinicalTrials.gov, number NCT00558896.
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]Pomalidomide (Imnovid®; Pomalyst®), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate. Pomalidomide plus low-dose dexamethasone had a manageable tolerability profile, with neutropenia, infections, anaemia and thrombocytopenia being the most frequently reported grade 3 or 4 treatment-emergent adverse events. In conclusion, pomalidomide plus low-dose dexamethasone extends the treatment options available for the management of relapsed and refractory multiple myeloma in a patient population that has very limited treatment options.
Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. [2015]Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma.
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]To establish the clinical use of bortezomib with fewer adverse events, we retrospectively analyzed the efficacy and safety of bortezomib plus dexamethasone (BD) therapy for relapsed or refractory multiple myeloma.
BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. [2022]Multiple myeloma remains incurable. Despite the pursuit of various chemotherapeutic approaches, little improvement in outcome has been made in the last 30 years. Thalidomide, dexamethasone, and clarithromycin are oral, nonmyelosuppressive agents, each with reported single agent activity against myeloma. We evaluated a regimen of clarithromycin (Biaxin), low-dose thalidomide and dexamethasone (BLT-D) in patients with previously untreated or treated multiple myeloma or Waldenström's macroglobulinemia. Patients were initially given clarithromycin 500 mg twice daily, thalidomide 50-200 mg daily, and dexamethasone 40 mg weekly until disease progression. Minimum response was defined as > 50% reduction in monoclonal immunoglobulin or light chain levels in serum or urine. Response, toxicity, and survival were determined on an evaluable and/or intent-to-treat basis. Of the 50 patients available for analysis, 92% remain alive and 64% remain on treatment with a median and mean duration of treatment of 7 and 8 months, respectively. Overall, 93% of evaluable patients responded to BLT-D, including 13% complete remissions, 40% near complete responses, 13% major responses, and 27% partial responses. Minimal drug resistance was initially encountered. Neurotoxicity, although usually mild to moderate, was the primary reason for treatment discontinuation. Only four patients died, including three sudden deaths in patients with severe cardiopulmonary disease. It appears that BLT-D is a highly effective, nonmyelosuppressive regimen for myeloma. Caution should be exercised when using thalidomide, alone or in combination, in patients with a preexisting tendency to thromboses, severe cardiopulmonary disease, or neurologic dysfunction.
A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. [2021]Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM.
Pomalidomide, Bortezomib, and Dexamethasone in Lenalidomide-Pretreated Multiple Myeloma: A Subanalysis of OPTIMISMM by Frailty and Bortezomib Dose Adjustment. [2023]A proportion of patients with multiple myeloma (MM) are older and/or have comorbidities, requiring dose adjustments. Data from OPTIMISMM (NCT01734928) supported the use of pomalidomide, bortezomib, and dexamethasone (PVd) for treating relapsed/refractory MM. This subanalysis of OPTIMISMM assessed outcome by frailty and/or bortezomib dose adjustment.
DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. [2022]Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).
Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. [2020]Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs.
Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. [2022]On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg.
Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]Belantamab mafodotin (belamaf) is a BCMA-targeted antibody-drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Belamaf binds to BCMA and eliminates myeloma cells by multimodal mechanisms of action. The cytotoxic and potential immunomodulatory properties of belamaf have led to novel combination studies with other anticancer therapies. Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma. Clinical trial registration: NCT04126200 (ClinicalTrials.gov).
Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. [2022]Estimate the budget impact of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.