Background The outlook for patients with metastatic synovial sarcoma (mSS) is poor. Better understanding of patient experience in this setting, beyond clinical measures, may guide improvements in management. Validated patient-reported outcome (PRO) instruments specific to many types of cancer exist, but for rare cancers this is often not the case. Methods This study aimed to characterize patient experiences of symptoms and impacts of mSS and evaluate the content validity and relevance of the novel European Organization for Research and Treatment of Cancer Item Library 31 (EORTC IL31) Disease Symptoms PRO tool assessing synovial sarcoma symptoms. This tool comprises items from preexisting, validated cancer-specific PRO instruments from the EORTC Item Library. It was developed as an mSS-specific add-on to the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), which evaluates general cancer and treatment-related symptoms and functioning. This was a non-interventional, qualitative interview study involving semi-structured, concept elicitation (CE) and cognitive debriefing (CD) telephone interviews in adults with mSS. CE explored symptoms and their impact on functioning and quality of life; CD assessed participant understanding and relevance of the PRO tools. Results Among the 8 participants, the most common disease-related symptoms reported during CE were fatigue and pain, while shortness of breath was one of the most bothersome. The greatest negative impacts of mSS occurred in domains of physical functioning and sleep. Key treatment priorities for patients were to improve disrupted sleep and ability to undertake strenuous activities. Conclusions The interviews showed that, when used together, the EORTC IL31 and EORTC QLQ-C30 covered symptoms and impacts of most relevance and importance to patients with mSS, with no notable gaps and good conceptual coverage. This study therefore supports the content validity of 2 tools in mSS, advocating their use in clinical trials to assess treatment impact on PRO measures of importance to these patients.

Introduction: Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In the pivotal Phase II DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (Lonial et al. Lancet Oncol 2020). Responses were sustained at 13 months of follow-up; with belamaf (2.5 mg/kg administered intravenously [IV] every 3 weeks [Q3W]), overall response rate (ORR) was 32% and median duration of response (DoR) was 11.0 months (Lonial et al. ASCO 2020 Poster 436). Preclinical data suggest synergistic antimyeloma activity of belamaf in combination with pomalidomide/dexamethasone (Pd). Preliminary data from an ongoing Phase I/II study (NCT03715478) evaluating belamaf in combination with Pd (B-Pd) suggest an acceptable safety profile and early signs of clinical activity in patients with RRMM. The DREAMM-8 study (NCT04484623) will evaluate the efficacy and safety of B-Pd compared with pomalidomide, bortezomib, and dexamethasone (PVd). Methods: This Phase III, two-arm, randomized, open-label, multicenter study will include patients with measurable RRMM who have received ≥1 prior line of therapy (including lenalidomide), with documented disease progression during or after their most recent line of treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ system function, and who provide informed consent will be eligible. Patients with prior exposure to BCMA-targeted therapies or pomalidomide and those intolerant/refractory to bortezomib will be excluded. Approximately 450 patients will be randomized (1:1) to Arm A (B-Pd) or Arm B (PVd), stratified by number of prior lines of treatment, prior exposure to bortezomib, and International Staging System status. No more than 50% of participants with two or more prior lines of treatment will be enrolled. In Arm A, patients will receive belamaf 2.5 mg/kg (IV) Q4W on Day 1 in Cycle 1 (28-day cycle) followed by belamaf 1.9 mg/kg (IV) Q4W on Day 1 in Cycle 2 onwards (28-day cycles); pomalidomide 4 mg (orally [PO]) will be administered on Days 1-21 and dexamethasone 40 mg (PO) on Days 1, 8, 15, and 22 in all cycles (28-day cycles). In Arm B, pomalidomide 4 mg (PO) will be administered Q3W on Days 1-14 in all cycles (21-day cycles); bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8, and 11 in Cycles 1-8, and Days 1 and 8 in Cycle 9+ (21-day cycles). Dexamethasone 20 mg (PO) will be administered on the day of and the day after bortezomib. The dose level of dexamethasone in each arm will be reduced by half in patients >75 years of age. Treatment in both arms will continue until progressive disease, unacceptable toxicity, withdrawal of consent, initiation of another anticancer therapy, or end of study or death. The primary endpoint is progression-free survival (PFS; time from randomization to the earliest date of documented disease progression or death [any cause]). Minimal residual disease negativity rate is a key secondary endpoint. Additional secondary endpoints include ORR, time to response, DoR, time to progression, overall survival, PFS2 (PFS after initiation of new anticancer therapy), safety, health-related quality of life, and pharmacokinetic and pharmacodynamic parameters. The study is planned to start in August 2020. Funding: GSK (Study 207499); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Trudel: GSK, Celgene, Janssen, Amgen, Genentech: Research Funding; Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding. Davis:GSK: Current Employment, Current equity holder in publicly-traded company. Lewis:GSK: Current Employment, Current equity holder in publicly-traded company. Bakshi:GSK: Current Employment, Current equity holder in publicly-traded company. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Eliason:GSK: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Wu:GSK: Current Employment, Current equity holder in publicly-traded company.

Introduction: Belantamab mafodotin is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody-drug conjugate (ADC) that is approved in the United States and European Union for adult patients with relapsed/refractory multiple myeloma (RRMM). In the pivotal Phase II DREAMM-2 study, single-agent belantamab mafodotin (2.5 mg/kg administered intravenously every 3 weeks [Q3W]) demonstrated an objective response rate of 32% with a manageable safety profile in triple-class refractory adult patients with RRMM (Lonial et al. Lancet Oncol. 2020). At 13 months of follow-up, responses were durable, with a median duration of response of 11 months and an overall survival of 13.7 months (Lonial et al. ASH 2020, Poster 1417). Corneal events are common and expected with belantamab mafodotin and other MMAF-containing ADCs. In DREAMM-2, keratopathy (a pathological eye exam finding) presented as superficial punctate keratopathy and/or microcyst-like epithelial changes. Ocular symptoms, such as decline in best-corrected visual acuity or patient-reported adverse events (eg, blurred vision or dry eye), were also common during treatment. Corneal events with or without symptoms were managed with dose modifications (delays and reductions), and clinically meaningful responses were observed even with prolonged treatment-free intervals; this suggests that alternative dosing regimens of belantamab mafodotin may lower rates of corneal events without compromising efficacy. The goal of the DREAMM-14 study is to investigate whether an improved overall benefit/risk profile of single-agent belantamab mafodotin can be achieved by modifying the belantamab mafodotin dose, schedule, or both relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, 5-arm, randomized, parallel, open-label multicenter study will include patients with RRMM who have received at least 3 prior lines of therapy including an anti-CD38 monoclonal antibody (mAb), an immunomodulatory agent, and a proteasome inhibitor. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status ≤2 and who provide informed consent will be eligible. Patients with corneal epithelial disease (except mild punctate keratopathy) or prior exposure to BCMA-targeted therapies or ADCs will be excluded. Patients will be randomized into Arms A to D (n=40 each) and arm E (n=20) in parallel and stratified by the International Staging System (ISS) for MM (I vs II vs III) and prior lines of therapy (3 vs ≥4). Single-agent belantamab mafodotin will be administered at doses and schedules as follows-Arm A: 2.5 mg/kg Q3W (control); Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index) and visual acuity. Participants in all arms will have Q3W response assessments and Q3W ophthalmic examinations and monitoring by qualified eye care specialists. Ocular event-related dose modifications for all arms except Arm E will be guided by the Keratopathy and Visual Acuity (KVA) scale. Participants in all arms will be treated until progressive disease, unacceptable toxicity, or death. The primary endpoint will be incidence of Grade ≥2 ocular adverse events according to the KVA scale. Key secondary endpoints include ocular safety and tolerability, pharmacokinetics, and efficacy outcomes of belantamab mafodotin in all arms. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Follow-up for overall survival will be Q12W from treatment discontinuation. The duration of this study will be approximately 22 months. The study is planned to start in the first quarter of 2022. Funding: GSK (Study 209628); drug linker technology licensed from Seagen; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Hultcrantz: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Curio Science LLC: Consultancy; Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding. Kleinman: Calm Water Therapeutics LLC: Current Employment; GlaxoSmithKline: Consultancy; Eyeon Therapeutics Inc.: Current holder of individual stocks in a privately-held company; ONL Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company; Triphase Accelerator: Consultancy; Helixmith Co., Ltd: Consultancy; Aprea Therapeutics: Consultancy; Editas Medicine, Inc.: Consultancy; Olema Pharmaceuticals, Inc.: Consultancy. Ghataorhe: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. McKeown: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; AstraZeneca: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. He: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ling: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Jewell: Alcon: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Brunner: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Byrne: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Adaptimmune: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Eliason: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Scott: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Opalinska: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company.