DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared with the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants with Relapsed/Refractory Multiple Myeloma (study 207503, DREAMM 7)

In relapsed or refractory multiple myeloma (RRMM), combination therapies
utilizing agents with differing modes of action have dramatically improved
outcomes. Combining active agents with bortezomib/dexamethasone (BOR/DEX)
treatment can yield improved patient outcomes with acceptable toxicity
profiles, establishing new global standard of care (SoC) regimens. The approval
of the anti-CD38 antibody daratumumab has demonstrated that the addition of a
targeted monoclonal antibody, with activity as a monotherapy, to BOR/DEX can
result in significant improvements in progression-free survival (PFS) in
patients with RRMM, and the combination of daratumumab with BOR/DEX is
currently a widely accepted SoC for MM patients who have received at least one
prior line of therapy.
Belantamab mafodotin (BM) has demonstrated strong single-agent activity in RRMM
in the First-Time-in-Human (FTIH) study. As of 31 August 2018, the Overall
Response Rate in 35 participants treated at the recommended Phase 2 dose of 3.4
mg/kg was 60.0% (95% CI: 42.1, 76.1) and the median PFS was 12.0 months (95%
CI: 3.1, NR) in a heavily pre-treated population (57% >=5 prior lines of
therapy). In participants refractory to both immunomodulators and proteasome
inhibitors (n=32/35), the ORR was 56% (95% CI: 37.7, 73.6).
In the FTIH study, the maximum clinical benefit was observed at the 3.4 mg/kg
dose level, but a significant number of participants required dose delays and
dose reductions to manage adverse events. In a phase II study, BM was further
evaluated as monotherapy in RRMM patients at the dose of 2.5 mg/kg and 3.4
mg/kg Q3W. Both dose levels have a positive benefit/risk profile. Overall,
there were no new safety signals identified in this phase II study. The dose of
2.5 mg/kg appears to have a lower incidence of adverse events and less dose
delays and reductions. It results in similar efficacy. The dose of 2.5 mg/kg
Q3W has been further evaluated in combination with bortezomib and dexamethasone
and based on the safety evaluation, this dose has been selected for this study.
It is hypothesized that the combination of BM and BOR/DEX will lead to greater
patient benefit, as measured by PFS, compared to the SoC combination of
daratumumab and BOR/DEX. While there are some potential overlaps in the pattern
of identified toxicities between BM and BOR/DEX (primarily hematologic), they
are expected to be manageable.

This study has been transitioned to CTIS with ID 2023-510537-28-00 check the CTIS register for the current data.

Primary:
To compare the efficacy of BM in combination with BOR/DEX with that of
daratumumab in combination with BOR/DEX in participants with RRMM
Secondary:
Other efficacy outcomes. Safety and tolerability. PK. Anti-drug antibodies.
Questionnaires (symptoms, quality of life).

Multicenter Phase III, randomized (1:1), open-label study evaluating the
efficacy and safety of the combination of BM and BOR/DEX versus the combination
of daratumumab and BOR/DEX in participants with RRMM.
Treatment cycles of 3 weeks (daratumumab after cycle 8: 4 weeks). I.V.
administration BM, daratumumab. S.C. administration of bortezomib.
Treatment until disease progression or unacceptable toxicity.
Approx. 600 participants.

Treatment with BM in combination with BOR/DEX or daratumumab in combination
with BOR/DEX.

Risk: Adverse events of the study medication.
Burden:
• Visits cycle 1-8 (4 to 5 times per cycle). Cycle 9+: once per cycle.
• Every 3 weeks an infusion with BM (I.V. infusion 250 mL in 30 minutes) or
every 3-4 weeks an infusion with daratumumab (I.V. infusion 500-1.000 mL in
approx. 5 hours).
• Physical examination: every cycle.
• Blood draws: every visit. 5-50 mL blood per occasion.
• ECG: once.
• Eye examination: cycle 1-4 and every 6 months thereafter.
• X-rays, CT/MRI scan: twice (to be repeated upon indication).
• BM aspirate/core biopsy: at screening and disease progression if not
otherwise demonstrable. After VGPR or CR every 6 months until CR/PD or PD resp.
• Questionnaires at screening, start, during treatment.
Optional:
• Blood sample for pharmacogenetics (6 mL).
• BM aspirate/core biopsy: once.