Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .

Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, demonstrated deep and durable responses with a manageable safety profile in patients with heavily pretreated RRMM (median 7 lines of prior therapy) refractory to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and refractory and/or intolerant to an anti-CD38 monoclonal antibody in the pivotal Phase II DREAMM-2 study (NCT03525678). At 13-month follow-up, the overall response rate (ORR) was 32% and the median duration of response (DoR) was 11.0 months in the belamaf 2.5 mg/kg arm (Lonial. ASCO 2020 Poster 436). The multimodal mechanism of action, efficacy and safety profile of belamaf, as well as preclinical data suggest possible synergy with standard of care agents and a potential benefit in combination with IMiDs and PIs. DREAMM-6 (NCT03544281) is an ongoing Phase I/II, two-part study of belamaf in combination with lenalidomide/dexamethasone (Arm A) or BorDex (Arm B) in patients with RRMM who had received ≥1 prior therapy (bortezomib-refractory patients were not excluded); preliminary results from Arm B have been reported (Nooka. ASCO 2020 Oral 8502). Methods: Part 1 (dose escalation) and Part 2 (dose expansion) of Arm B in DREAMM-6 evaluated belamaf (2.5 and 3.4 mg/kg intravenously (IV) every 3 weeks [Q3W]) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) plus BorDex (Bor 1.3 mg/m2 [subcutaneously] and Dex 20 mg [IV or orally]). Combination treatment continued for up to 8 cycles, with single-agent belamaf maintenance therapy thereafter. Primary objectives were safety, tolerability, and efficacy (ORR [≥ partial response, PR] per investigator-assessed best confirmed response). We report safety and efficacy results from the 2.5 mg/kg SINGLE dose cohort from Arm B. Results: As of March 30, 2020, 18 patients had received belamaf 2.5 mg/kg SINGLE + BorDex in Parts 1 and 2 of Arm B. The median age was 67 years, 61% were male, and 33% had high-risk cytogenetics; patients had received a median of 3 (range, 1-11) prior lines of therapy. All 18 patients had treatment-related adverse events (AEs), of whom 16 (89%) had Grade 3/4 events (see Table). Treatment-related serious AEs occurred in 5 (28%) patients. There were no Grade 5 AEs of interest. Thirteen (72%) patients had dose reductions (8/13 belamaf) and all patients had dose delays (16/18 belamaf) to manage AEs. Five (28%) patients discontinued a study treatment due to AEs: 4 bortezomib, 2 dexamethasone, no patients discontinued belamaf. Of the AEs of interest, thrombocytopenia occurred in 12 patients (67%; maximum Grade 4 in 8 patients and Grade 3 in 3 patients) and led to dose reduction in 6 (33%) patients, dose delay in 7 (39%) patients, and no discontinuations. Three (17%) patients had Grade 2 infusion-related reactions (with no dose modifications or discontinuations). Changes in the corneal epithelium (keratopathy/microcyst-like epithelial changes [MECs], an eye exam finding with or without symptoms), an anticipated AE associated with monomethyl auristatin F, the payload in belamaf, occurred in all 18 patients (maximum Grade 3 in 10 patients, Grade 2 in 7 patients, and Grade 1 in 1 patient), and led to dose reduction in 7 (39%) patients, dose delay in 15 (83%) patients, with no discontinuations. Response was evaluable in all patients; ORR was 78% (95% CI 52.4-93.6), with very good partial response (VGPR) in 9 (50%) and PR in 5 (28%) patients. One (6%) patient had minimal response, and 3 (17%) patients had stable disease. Clinical benefit rate was 83% (95% CI 58.6-96.4). After a median of 18.2 weeks (range 6.0-46.4 weeks) on treatment, median DoR was not reached. Conclusions: The combination of belamaf 2.5 mg/kg Q3W with standard-of care BorDex demonstrated an acceptable safety profile in patients with RRMM who had received a median of 3 prior lines of therapy, with AEs as expected, and no new safety signals to date. Corneal events were common but manageable with belamaf dose modifications. At interim follow-up, best response data indicate a high ORR of 78%, VGPR of 50%, and clinical benefit rate of 83%. Final data for the 2.5 mg/kg SINGLE + BorDex cohort will be reported at the congress. Funding: GSK (Study 207497); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Disclosures Popat: AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Nooka:Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Stockerl-Goldstein:Celgene: Consultancy; Abbott Laboratories: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company; GSK: Research Funding; Takeda: Research Funding; BiolineRx: Research Funding; Janssen: Research Funding; Cellerant: Other: Other relationship. Abonour:Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding. Khot:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Other: Speaker fees; Novartis: Other: Travel grant. Lee:Janssen: Consultancy; Amgen: Consultancy; Celgene/BMS: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Spencer:AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Celgene, Janssen and Takeda: Speakers Bureau. Mateos:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; PharmaMar-Zeltia: Consultancy; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rogers:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Smith:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Davidge: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. Yeakey:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Talekar:GlaxoSmithKline: 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. Quach:Sanofi: Consultancy, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding.