DREAMM-4: evaluating safety and clinical activity of belantamab mafodotin (belamaf) in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma: Session: Multiple Myeloma
Bibliographic record
Abstract
Introduction: Single-agent belamaf (GSK2857916; BLENREP) has shown deep and durable responses and a manageable safety profile in patients with heavily pretreated RRMM (DREAMM-2, NCT03525678, Lancet Oncol 2020). Immune surveillance in patients with RRMM is often blunted through the PD-1/PDL-1 axis; PDL-1 being highly expressed on MM cells. PD-1 inhibitor pembrolizumab, may augment immune responses to belamaf-induced immunogenic cell death. DREAMM-4 (NCT03848845) is an ongoing Phase I/II, two-part study assessing safety and efficacy of belamaf plus pembrolizumab in patients with RRMM. Methods: Patients had ≥3 prior lines of therapy, including anti-CD38 treatment. Planned enrollment for both parts is up to 40 patients. Part 1 (dose escalation) evaluates 2.5 or 3.4 mg/kg belamaf plus 200 mg pembrolizumab in up to 12 patients to establish the recommended Phase II dose (RP2D) of this combination. Both drugs are given IV Q3W for up to 35 cycles. Part 1 interim analyses (IA) are presented. Part 2 (dose expansion) will confirm safety and assess clinical activity at the RP2D; overall response rate (ORR; ≥partial response) is the primary endpoint. Results: As of 4 Feb 2020, 6 and 7 patients were enrolled at the 2.5 and 3.4 mg/kg doses, respectively (1 patient replaced as per protocol). In the 2.5 and 3.4 mg/kg groups, median (range) prior lines of therapy were 7.5 (3–13) and 5.0 (3–8), and 3/6 (50%) and 1/7 (14%) patients had high-risk cytogenetics. No dose-limiting toxicities were reported in either group. All patients in both groups experienced adverse events (AEs) and treatment-related AEs. The most frequent AEs of any grade and Grade 3/4 are reported in the Table. Serious AEs (SAEs) were reported in 50% (3/6) of patients in the 2.5 mg/kg group (n=1 had a treatment-related SAE) and 43% (3/7) of patients in the 3.4 mg/kg group (n=3 had a treatment-related SAE). No Grade 5 AEs occurred. Keratopathy (microcyst-like epithelial changes [MECs], with/without symptoms) was the primary reason for dose delays (2.5 mg/kg group: 67%; 3.4 mg/kg group: 14%) and dose reductions (2.5 mg/kg group: 17%; 3.4 mg/kg group: 0%). The ORR was 67% and 14% in the 2.5 and 3.4 mg/kg groups, respectively (Table). PK data and free soluble BCMA levels were consistent with previous studies. Conclusion: Belamaf plus pembrolizumab demonstrated a manageable safety profile and clinical activity in patients with RRMM. Keratopathy (MECs) was the most frequent AE, consistent with belamaf studies, and managed with dose modifications. Part 1 IA supports continuation with Part 2 of this study. Funding: GSK (205207) in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT technology licensed from BioWa. Encore Statement: This abstract was accepted and previously presented at EHA 2020 (Nooka et al EP955). Resubmitted with permission.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".